The Sentinel

THE OFFICIAL BLOG OF THE SOCIETY FOR IMMUNOTHERAPY OF CANCER (SITC).

Tuesday, May 7, 2019

President's Message - May 2019

Dear Colleagues,

The Society for Immunotherapy of Cancer (SITC) hosts dozens of educational and scientific meetings each year to support the primary mission of the society, which is to improve cancer patient outcomes by advancing the science and application of cancer immunotherapy. In this letter I bring to your attention this year’s interim workshops, which provide a forum to address specific important and evolving areas in our field. The workshops will focus on cancer immune responsiveness and adoptive cellular therapies and will be organized by prominent members of the immuno-oncology community, including Alessandra Cesano, MD, PhD (NanoString Technologies, Inc.), Francesco M. Marincola, MD (Refuge Biotechnologies, Inc.), and Katayoun Rezvani, MD, PhD (The University of Texas MD Anderson Cancer Center).

Both multi-day programs will bring together some of the foremost experts and future leaders in the science and clinical application of immune therapies. Participants will review current progress as the basis to initiate discussions of challenges and potential solutions to advance the field. The assembled researchers and clinicians usually produce a formal output from the meeting, often published in the Journal for ImmunoTherapy of Cancer (JITC), the society’s open access, peer-reviewed online journal.

On Sept. 4-5, 2019, in Houston, Texas, the SITC Cancer Immune Responsiveness Task Force will, for the second consecutive year, host a Cancer Immune Responsiveness Workshop. The focus on understanding cancer immune responsiveness is timely and critical for our field, and could lead to improved prognostic and predictive biomarkers, improved patient selection, more rational combination strategies in the clinic and more efficient clinical development of single agents and combinations. Didactic lectures and working groups will cover key topics such as the role of host genetics and epigenetics in immune responsiveness; transcription patterns indicative of distinct tumor immune landscapes; and more. Immediately following, on Sept. 5-6, 2019, SITC will host the Adoptive Cellular Therapies Workshop. The field of adoptive cell therapy is receiving increased attention from scientists, clinicians, patients, regulators and payors following the 2017 U.S. Food and Drug Administration approval of Chimeric Antigen Receptor (CAR) T cell therapies for patients with lymphoma and leukemia. This is, in my opinion, one of the most exciting and promising areas of clinical medicine, and this program will bring together experts to address the evolving science of cell engineering, novel strategies to improve the overall risk/benefit profile, clinical development, regulatory challenges and more.

Additionally, three collaborative sessions, taking place the morning of Sept. 5, will allow attendees from both workshops to discuss common challenges of the field and new concepts that impact cancer immune responsiveness and adoptive cellular therapies.

Please consider joining us for both programs over the course of three days. Participants who register for both workshops will receive a 30 percent discount.

Finally, for those attending the 2019 American Society of Clinical Oncology Annual Meeting in Chicago, I hope you consider joining me, the SITC staff and your fellow SITC colleagues and friends at SITC’s annual fundraiser for the Forward Fund, The CheckPoints Party. Come and party with the Checkpoints band (stars in the true sense of the word, including 2018 Nobel Laureate James P. Allison, PhD) beginning at 8 p.m. on Sunday, June 2, at Buddy Guy’s Legends (700 S. Wabash Ave., Chicago).

VIP tickets are available online or by calling 414-271-2456. General admission at the door is available on a first-come, first-served basis, with suggested donation of $30. Proceeds support SITC’s Forward Fund, providing grant opportunities to promising early career scientists in the field. You can learn about some of the young investigators who have benefited from the SITC Forward Fund by viewing the Faces of the Forward Fund.

Sincerely,















Mario Sznol, MD
SITC President

Tuesday, April 9, 2019

President's Message - April 2019

Dear Colleagues,

I wish you all a happy spring. While I certainly do not hope for the next seven months to speed by, the Society for Immunotherapy of Cancer’s 34th Annual Meeting & Pre-Conference Programs (SITC 2019), to be held Nov. 6–10, will no doubt be here before we know it. Registration is already open for SITC members (and opens for all on April 9). This is our society’s cornerstone conference, and this year we return to the Gaylord National Hotel & Convention Center in National Harbor, Md. I am already excited to see and welcome back existing members and to meet the new members of our Society.

Last year, 5,000 professionals in the cancer immunotherapy field attended our Annual Meeting & Pre-Conference Programs, a 36 percent increase over 2017. Similarly, we received nearly 800 abstract submissions, a 34 percent increase year-over-year. For me personally and I’m sure for all of us involved in the Society, it has been astounding to witness the growth of our annual gathering of basic scientists, translational researchers, clinicians, industry and governmental representatives and others in recent years.

This year, the Annual Meeting will feature several new oral abstract presentation opportunities. Increasing the number of oral presentations has been a key goal of our Board for several years, affording researchers, and in particular younger investigators, additional time to share the findings of their work and connect to others in the field. First is a Poster Symposium on Thursday, Nov. 7, from 5:30 – 7:30 p.m., which will comprise several short abstract presentations and expert discussants. Secondly, the number of rapid oral abstract sessions has doubled; two sessions will be held on Friday and two on Saturday. Half of these rapid oral abstract sessions will feature clinical advances in the field. Finally, three designated clinical trial sessions will ensure the conference captures the important clinical trial work being done in the field:
  • High Impact Clinical Trials: Friday, Nov. 8, 4:50-6:15 p.m.
  • Single Agent Phase 1 Clinical Trials: Saturday, Nov. 9, 3:45-5 p.m.
  • Combination Phase 1-2 Clinical Trials: Saturday, Nov. 9, 5:15-6:30 p.m.
More than 16 months of planning and preparations go into each Annual Meeting. Dedicated committee members, lead by Annual Program Committee Chair Sandra Demaria, MD (Weill Cornell Medicine), and assisted by the Board of Directors and faculty, work tirelessly to ensure program schedules contain impactful data and meaningful panel discussions. It’s this devotion and enthusiasm that brings the highest quality data to the SITC’s Annual Meeting & Pre-Conference Programs. For immune therapy of cancer, I believe it is the most influential conference in the field.

Please join me in congratulating our recently announced 2019 Richard V. Smalley, MD, Memorial Award and Lectureship recipient Olivera (Olja) J. Finn, PhD, of University of Pittsburgh School of Medicine. Dr. Finn will deliver her highly anticipated keynote address during the Annual Meeting, on Friday, Nov. 8. I’m also very pleased to announce that Ronald N. Germain, MD, PhD, of the National Institutes of Health, will deliver Saturday’s keynote address.

Please remember that SITC members receive discounted SITC 2019 registration rates and early access to housing. There are so many reasons to become a SITC member, and the savings for attending just part of SITC 2019 will more than cover the cost of a membership. So don’t wait, join SITC today to save on your SITC 2019 attendance.

Although our Annual Meeting & Pre-Conference Programs is our most highly attended program, we offer a variety of other opportunities for education and scientific exchange throughout the year, including interim workshops. Two exciting and timely 2019 workshops – dedicated to cancer immune responsiveness and adoptive cellular therapies – are scheduled for Sept. 4–6, 2019, in Houston, Texas, and registration is now open. Participants who attend both back-to-back workshops will receive a 30 percent discount on registration.

Sincerely,















Mario Sznol, MD
SITC President

Tuesday, March 5, 2019

President's Message - March 2019

Dear Colleagues,

Last month, the Society for Immunotherapy of Cancer (SITC) recognized and celebrated International Day of Women and Girls in Science. With International Women’s Day approaching (March 8), it reminds us of our responsibility and commitment to help advance the careers of women in the cancer immunotherapy field.

As the successor to the Society for Immunotherapy of Cancer’s (SITC) first female president, Lisa H. Butterfield, PhD, I am privileged to continue and expand our society’s support of women involved with research and development in the laboratory, clinic, industry and all other areas related to immuno-oncology.

Dr. Butterfield championed many causes, programs and initiatives during her tenure as SITC President, including working to ensure the society was recognizing and encouraging professional development for women. This included hosting women’s receptions at the past two SITC Annual Meetings, offering women an opportunity to network, celebrate successes and discuss important topics critical to their advancement.

Through Dr. Butterfield’s continued leadership, and with support from many of our fellow colleagues, SITC will host its first-ever Women in Cancer Immunotherapy Network (WIN) Leadership Institute this summer. Scheduled for Aug. 19–20, 2019, in Seattle, the SITC WIN Leadership Institute will provide a forum for attendees to discuss important topics relevant to their advancement, including how to break through the glass ceiling; negotiation tactics; and critical leadership skills. Also of note, the program is free to attend. Women interested in attending this exciting one-and-a-half-day program are encouraged to submit an application by April 15.

SITC is currently recruiting our members to join the Women in Cancer Immunotherapy Network Database. This database will contain a repository of leaders in the field of cancer immunotherapy with an interest in serving as subject matter experts for a variety of potential roles, such as presenting data at SITC meetings, conducting article reviews for the Journal for ImmunoTherapy of Cancer (JITC), serving in organizer roles to plan future meetings and more.

Those interested in being considered for such future opportunities can submit their credentials via the SITC Volunteer Portal, a members-only benefit. If you have questions about the database, please contact Senior Administrative Manager Rosanne Stelpflug.

I, along with all the leadership of SITC, wholeheartedly support the efforts of the WIN. The WIN is a key part of our society’s commitment to developing future female leaders in science and medicine – some who will hopefully follow Dr. Butterfield’s footsteps and serve as SITC President in the future. I’m also sending a reminder that SITC member registration for the 34th Annual Meeting & Pre-Conference Programs (SITC 2019) opens soon – on March 26. Scheduled for Nov. 6–10 in National Harbor, Md., SITC 2019 will take our society to new heights and I look forward to seeing new and familiar faces this fall.

Sincerely,















Mario Sznol, MD
SITC President

Tuesday, February 5, 2019

President's Message - February 2019

Dear Colleagues,

As I enter my second month as President of the Society for Immunotherapy of Cancer (SITC), I am energized in our society’s efforts to continue our growth and success into this new year. As we set the stage for the future, I wanted to offer a brief history of SITC for those new to the society, to acknowledge and celebrate our past, all made possible by a dedicated (and growing) family of SITC members.

SITC was originally founded in 1984 by 40 charter members as the Society for Biological Therapy (SBT). At the time, enthusiasm for cancer immunotherapy was driven by investigations of early cancer vaccines, interferons, interleukin-2 and other types of immune modulators. Fundamental discoveries in molecular biology and immunology over the ensuing years provided the foundation for advances in cancer immunobiology, and consequently ushered in the modern era of cancer immunotherapy, which includes transforming therapies such as the immune checkpoint inhibitors and CAR-T cells. Members of our Society were key drivers of many of these advances, in the lab and the clinic, and through critical roles within industry and government.

I attended my first meeting of the society, then SBT, in approximately 1989, and witnessed the rapid advances in understanding the nature of host anti-tumor immunity over the next decade. Based on a growing body of exciting preclinical data, many agents were brought to clinical trials by dedicated researchers, although with limited clinical success. Nevertheless, members of our society remained steadfast in their efforts to develop highly effective cancer immunotherapies. During the SBT 2002 business meeting, members voted to officially change our name to the International Society for Biological Therapy of Cancer (iSBTc). This change was enacted so that our name would reflect our emphasis and concentration on cancer while embracing and valuing our expanding member footprint across the globe. We experienced further change in 2010 when members voted to refresh the name to the Society for Immunotherapy of Cancer, a moniker that captures our focus and expertise.

The field as a whole, and our society more specifically, has come a long way in the past 35 years. Immunotherapy is not only a viable alternative to other treatments, but now in many malignancies, the most important component of treatment for cancer patients. Improved patient response rates and overall outcomes have undoubtedly played a substantial role in our society’s growth and prosperity, particularly in the past seven years. Since 2012, SITC membership has grown more than 300 percent, from 601 members to 2,457 in 2018.



The diversity of our membership has grown over the years and our society adjusted to reflect the change in composition, adding categories of nurses, pharmacists and patient advocates in recent years. In total, SITC maintains eight member categories for professional and personal classification purposes:

  • Regular
  • Affiliate
  • Emeritus
  • Nurse and Advanced Practice Provider
  • Patient
  • Patient Advocate
  • Pharmacist
  • Student and Scientist-in-Training


Historically and to this day, our regular member category is our most popular, growing to more than 1,600 professionals in the field in 2018, including basic and translational scientists and practicing oncologists. I find it interesting that while the number of regular members has increased by nearly 450 in the past three years, the category’s representation within the overall SITC membership body has actually declined by three percent since 2016. All other member categories – save emeritus, which has remained steady, comprising 18 members – have increased during the same timeframe, suggesting our reach and effect on the greater cancer community continues to grow. It is clear, though, that once a regular member joins SITC, they find a home in our society, as our retention rate among this category is a staggering 88 percent.

While we know that access to discounted registration rates at SITC programs remains a valued member benefit, our members repeatedly tell us that the ultimate rewards of a SITC membership are the indispensable professional relationships built through society involvement. These relationships expand professional networks and set the stage for meaningful collaborations that spark the next advances in the field, all with the same goal of improving patient outcomes.

I appreciate each and every one of our society’s members, many who have already renewed their memberships for the balance of 2019. Continue reading this month’s Immune Monitor to learn more about the value of a SITC membership. If you’re not currently a member, I encourage you to consider becoming a part of the SITC family.

Sincerely,















Mario Sznol, MD
SITC President

Tuesday, January 8, 2019

President's Message - January 2019

Dear Colleagues,

I am excited and honored to address you in my first monthly message as President of the Society for Immunotherapy of Cancer (SITC). I have enjoyed the past two years as SITC’s Vice President, supporting Lisa H. Butterfield, PhD, SITC’s first female president, during her tenure as leader of our society. Thank you, Dr. Butterfield, for setting a foundation for the increased inclusion, development, and celebration of women in cancer immunotherapy. The society appreciates your continued leadership and commitment to the field and our organization!

As I assume this role on the heels of another successful year for SITC – which includes reaching new marks within our membership and a record-breaking 5,000 attendees at our Annual Meeting & Pre-Conference Programs – I am looking forward to helping continue our society’s tremendous growth. During my tenure as President, I will work to sustain SITC’s commitment as the leading member association in cancer immunotherapy. I will also ensure SITC remains the host to the most important meeting in the field, as we provide a platform for the presentation of phase 1 clinical trial data that provide insight into the future of immuno-oncology.

SITC has many exciting programs and initiatives slated for the next 12 months, all of which seek to improve cancer patient outcomes by advancing the science, development and application of cancer immunotherapy. A more complete listing of these initiatives is provided below, and I would like to highlight a few occurring in the near future.

It is critical for SITC to continue its emphasis in growing the next generation of leaders in cancer immunotherapy and tumor immunology. This is an area I am keenly focused on and support heavily. To that end, SITC is pleased to continue to offer SITC Fellowship Awards in 2019. Made possible through generous support from our industry partners, SITC Fellowships honor some of the brightest young minds in the field. The development and celebration of young investigators in our field is an important strategic priority of the society and one of my foci as President.

Additionally, registrations are open for SITC’s first Cancer Immunotherapy Winter School. Scheduled for Feb. 18-22 in Mesa, Ariz., this new program, tailored to early career scientists and clinicians as well as those new to the field, will teach the fundamentals of cancer immunotherapy and allow attendees to choose from a variety of tracks that focus on topics most relevant to them. Space is limited so register early! Also, SITC will host its first Meet-the-Expert Webinar on Thursday, Jan. 17 at 12:30 p.m. CST. This hour-long webinar, moderated by Sruthi Ravindranathan, PhD (Emory University), and with participation from presenter Vionnie W.C. Yu, PhD (Novartis Institutes for Biomedical Research), will focus on the topic Careers in Industry. Please click here to register for this free online event.

SITC continues its 2018-19 Advances in Cancer Immunotherapy™ (ACI) regional education program series, with events currently confirmed for Sacramento, Calif., on Jan. 10 in Houston on Feb. 9 and in Portland, Ore., on Feb. 21. Also, we look forward to hosting two, back-to-back thoughtful and engaging interim workshops, focused on cancer immune responsiveness and resistance; and adoptive cellular therapy. Stay tuned for information regarding location, registration and lodging.

If you haven’t already, I hope you’ll consider joining or renewing your SITC membership in 2019 to enjoy a variety of member benefits, including early access to register for the 34th Annual Meeting & Pre-Conference Programs, scheduled for Nov. 6-10, 2019, in National Harbor, Md.

I am excited to strengthen existing, and build new, relationships with leaders in the field as we work together to continue the growth and success of the society.

Sincerely,















Mario Sznol, MD
SITC President

Thursday, December 6, 2018

President's Message - December 2018

Dear Colleagues,

In my final Society for Immunotherapy of Cancer (SITC) Presidential Message, I thought I’d start with last month’s 33rd Annual Meeting & Pre-Conference Programs (SITC 2018). We welcomed 5,000 attendees; the society’s highest number to date. Also, SITC now has more than 2,400 society members – the highest number in our history, including researchers, clinicians, patient advocates and students. I would be remiss if I did not express my sincere appreciation to all of our funders who contributed to our success by supporting our many educational programs in 2018. The full list appears below. It has really been an extreme period of growth, both within our society as well as the field in general, and support from our partners has been instrumental.

It has been an honor and a pleasure to serve as SITC President, for these last two years, and I look forward to the leadership of Mario Sznol, MD, as incoming President and to continuing to participate in society leadership as Immediate Past President for two more years. This position has allowed me to participate in many field-wide initiatives around both the science (immune biomarkers, SITC Cancer Immunotherapy Winter School, immune responsiveness, cellular therapies, the SITC textbook) and the people in it (women’s networking, young investigators, international outreach, among others). It has put me around the table with my academic colleagues, pharma and biotech collaborators, leaders of related societies and NCI and FDA colleagues to discuss how we can work together towards our shared goals of meaningful science and therapies for patients. All of this work has been enabled and supported by all of you, the staff of SITC and especially Tara Withington, CAE, SITC’s Executive Director.

There has been important progress in the last several years, and there is much more to do. SITC will be a vehicle supporting progress for years to come, and I look forward to working with you all to make it happen.

Sincerely,














Lisa H. Butterfield, PhD
SITC President

Monday, November 12, 2018

SITC 2018 Scientific Highlights - Nov. 11

The Society for Immunotherapy of Cancer (SITC) is pleased to present scientific highlights from the Nov. 11, 2018, sessions of the 33rd Annual Meeting.

 

Phase 1b/2 Data Suggest Promising Efficacy and Safety of Anti-NKG2A Monalizumab in Combination with Cetuximab for the Treatment of Patients with Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck  


Roger Cohen, MD (Abramson Cancer Center, Philadelphia, PA, USA), reported on a phase 1b/2 clinical trial (NCT02643550) evaluating the safety and efficacy of anti-NKG2A monalizumab in combination with cetuximab in patients who have received prior systemic therapy for recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). As of August 31, 2018, 40 total patients were enrolled (Progressive disease after platinum, 75 percent are HPV negative, 43 percent prior IO therapy, 33 percent are IO resistant) and received monalizumab (10 mg/kg Q2W) in combination with cetuximab (400 mg/m2). Median overall survival (OS) was 10.3 months and 12.8 months in IO naïve (n=23) and prior IO patients (n=17), respectively. Median progression-free survival (PFS) was 4.0 months and 5.0 months in IO naïve and prior IO patients, respectively. Overall response rate (ORR) was 27.5 percent (95 percent CI, 16.1-42.8) in all patients with one confirmed complete response (CR) and ten confirmed partial responses (PR). Responses to therapy were observed in both IO naïve (35 percent [95 percent CI: 19 – 55]) and IO pretreated patients (18 percent [95 percent CI: 6 – 41]). Median duration of response (DOR) was 5.6 months (95 percent CI: 3.8 – not yet reached). Combination-related adverse events (AEs) were mostly grade 1-2. Only one patient required cessation of treatment secondary to treatment related toxicity, with no observed potentiation of cetuximab-related AEs. Additionally, stromal NK cell and tumor CD8+ T cell infiltration was observed 15 days after first administration of combination treatment in all responding patients. Together, these data suggest combination monalizumab and cetuximab is safe and may be effective in treating patients with both IO naïve and IO pretreated R/M SCCHN. 

OX40 and CD137 Dual Agonist Bi-specific Antibody FS120 mAb2 Activates T cells and Promotes FcγR-independent Anti-tumor Activity in Pre-clinical Models


Miguel Gaspar, PhD (F-star Biotechnology, Cambridge, UK), described the anti-tumor activity of FS120 mAb2 – a bi-specific antibody that targets the co-stimulatory tumor necrosis factor receptor (TNFR) superfamily receptors OX40 and CD137. OX40 and CD137 are expressed on CD4+ and CD8+ T cells as well as NK cells, suggesting that the ligation of the receptors may help activate various types of immune cells. However, FcγR-mediated crosslinking is also necessary for monoclonal antibodies to induce receptor clustering and immune activation. To overcome this issue, FS120 mAb2 was generated by introducing an OX40-binding site into the Fc-region of a human IgG1 targeting CD137. Data indicate FS120 mAb2 concurrently binds to OX40 and CD137 in pre-clinical models with subnanomolar affinity and stimulates both CD4+ and CD8+ T cells in the absence of FcγR crosslinking. FS120 mAb2 demonstrated increased anti-tumor activity than a combination of OX40 and CD137 monoclonal antibodies in the CT26 mouse tumor model (p less than 0.00001). In addition, doses as low as 1 mg/kg of FS120 mAb2 induced peripheral T cell activation and proliferation without regulatory T cell depletion in CT26 and B16-F10 syngeneic models. Together, these data suggest that FS120 mAb2 can stimulate both CD4+ and CD8+ T cells, mediating potent FcγR-independent anti-tumor activity, and support initiation of future clinical development.  

Pre-clinical Studies Suggest Removal of Terminal Sialic Acids of Sialoglycans with EAGLE may Enhance Anti-PD-1 Efficacy 


Li Peng, PhD (Palleon Pharmaceuticals, Waltham, MA, USA), presented research describing EAGLE (enzyme-antibody glycan-ligand editing) - a novel multi-functional antibody-like molecule that inhibits the glyco-immune checkpoint axis by selectively removing the terminal sialic acids of sialoglycans on tumor cells. Recent data suggest that the glyco-immune checkpoint axis (sialoglycan/Siglec pathway) may serve as a target to alter immunity within tumor microenvironment. Ligation of sialylated glycans to ITIM (immune receptor tyrosine-based inhibitory motif)-containing Siglecs on immune cells regulates functions of macrophages, monocytes, dendritic cells, T cells, and NK cells. In this study, multiple EAGLE variants were shown to reduce tumor growth in mice bearing EMT6-Her2 syngeneic subcutaneous/orthotopic breast cancer tumors, achieving 7/24 CR. Further experiments revealed that EAGLE treatment decreased sialic acid levels on tumor cells, leading to increased immune cell infiltration and activation as well as induction of anti-tumor immunological memory. EAGLE pre-clinical efficacy was reduced by depletion of NK cells, macrophage, and CD8+ T cells. Interestingly, treatment with EAGLE or the combination of anti-PD-1 and anti-CTLA4 achieved similar anti-tumor activity in mice bearing the “cold” poorly immunogenic B16D5-Her2 tumor model. Importantly, EAGLE + anti-PD-1 was more effective at eradicating tumors than the respective monotherapies (6/6 CR = EAGLE + anti-PD-1, 3/6 CR = EAGLE, 2/6 = anti-PD-1). These data demonstrate pre-clinical efficacy of EAGLE as a monotherapy and in combination with anti-PD-1, and suggest that EAGLE may favor induce immunity against “cold” tumors. 

Novel Hexavalent Fusion Protein HERA-GITRL Promotes T cell Expansion and Anti-tumor Activity in Humanized Mouse Models 


David Richards, PhD (Apogenix AG, Heidelberg, Germany), presented data detailing the effects of HERA-GITRL - a hexavalent human glucocorticoid-induced tumor necrosis factor receptor (TNFR) ligand fusion protein - to increase T cell stimulation and subsequent anti-tumor activity. Pre-clinical data indicate that agonizing the TNFR super family member GITR can induce anti-tumor T cell activation and may be a promising cancer immunotherapy strategy. HERA-GITRL is composed of a trivalent single chain GITRL-receptor-binding-domain fused to an IgG1-derived silenced Fc-domain that serves as a multimerization scaffold. In vitro analyses showed that HERA-GITRL increases activation, maturation, and proliferation of CD4+ and CD8+ T cells, naïve and memory T cells, without affecting regulatory T cells (Tregs), and can prevent Treg-mediated suppression. In pre-clinical in vivo antigen-specific adoptive transfer assays, surrogate murine HERA-GITRL (5 mg/kg) increased expansion of antigen-specific CD4+ and CD8+ T cell populations compared to control treatment (CD8+ = 3.5 percent vs 1.3 percent; CD4+ = 4.2 percent vs 2 percent), and did not stimulate non-specific immune cell expansion. Treatment of CT26 cancer models with HERA-GITRL (1mg) reduced tumor growth compared to placebo. HERA-GITRL-mediated T cell activation enhanced tumor cell killing independent of Fc functionality in vitro as well as in humanized mouse models. These pre-clinical data suggest that HERA-GITRL may be able to enhance antigen-specific T cell activity and anti-tumor efficacy.