JITC Letter from the Editor - June 2019

Dear JITC Readers,

In the June edition of the JITC Digest, I would like to draw special attention to the following articles. First, “Carboplatin/paclitaxel, E7-vaccination and intravaginal CpG as tri-therapy towards efficient regression of genital HPV16 tumors” by Sonia Domingos-Pereira et al. investigates the effects of systemic administration of a chemotherapy doublet in combination with HPV16-E7 synthetic long peptide (E7LP) vaccination, followed by intravaginal immunostimulation in the genital orthotopic TC-1 mouse model. Results from this study suggest that combining novel vaccine formulations with local immunostimulation and standard-of-care chemotherapy have the potential to benefit patients with HPV-associated cancer.

Next, the research article “Selectively hampered activation of lymph node-resident dendritic cells precedes profound T cell suppression and metastatic spread in the breast cancer sentinel lymph node,” by Kim M. van Pul et al. describes the immune status of breast draining lymph nodes (LN) in a quantitative and functional manner using multi-parameter flow cytometry and ex-vivo cultures, and compares it with that of breast-draining axillary LN from healthy donors. This study provides new insights into the mechanisms underlying loco-regional immune suppression in breast cancer and how this relates to clinical parameters and suggests that LN-resident-conventional dendritic cells are potential therapeutic targets.

Furthermore, the article, “Anti-pancreatic tumor efficacy of a Listeria-based, Annexin A2-targeting immunotherapy in combination with anti-PD-1 antibodies,” by Victoria M. Kim et al. shows for the first time, that a Listeria vaccine-based immunotherapy was able to induce a tumor antigen-specific T cell response within the tumor microenvironment of a “cold” tumor such as PDAC and further sensitizes the tumor to checkpoint inhibitor therapy. This combination immunotherapy led to objective tumor responses and survival benefit in mice with spontaneously developed PDAC tumors, supporting Lm-ANXA2 as a therapeutic agent in combination with anti-PD-1 antibody for PDAC treatment.

“Neurologic toxicity associated with immune checkpoint inhibitors: a pharmacovigilance study,” by Douglas B. Johnson et al. leverages Vigibase, the World Health Organization pharmacovigilance database, to further define neurologic toxicities in the largest characterization of neurologic immune-related adverse events (irAEs) associated with ICIs. Results of this analysis pinpointed several categories of neurologic toxicities strongly associated with CNS inflammation or peripheral neuromuscular autoimmune disorders of which clinicians should be aware of in administering checkpoint blockade.

Finally, Hyun Gul Yang et al.’s article, “Discovery of a novel natural killer cell line with distinct immunostimulatory and proliferative potential as an alternative platform for cancer immunotherapy,” presents a novel NK cell line, NK101, from a patient with extra-nodal NK/T cell lymphoma and an assessment of its phenotypic, genomic and functional characteristics, with results suggestive of its therapeutic application as a CAR T-alternative anti-cancer cellular platform with improved efficacy and superior scalability.

With best regards,

Pedro J. Romero, MD
Editor-in-Chief, Journal for ImmunoTherapy of Cancer

To view the entire June 2019 JITC Digest, please click here. 

Q&A with SITC Vice Presidential Candidate Patrick Hwu, MD

In celebration of Cancer Immunotherapy Month™, we’ve asked SITC leaders to participate in a Q&A series for The Sentinel. We’ve asked them to briefly share why they entered the field, advice they’d share with early career scientists considering a career in cancer immunotherapy and more.

Please see below the Q&A from Patrick Hwu, MD, of University of Texas MD Anderson Cancer Center. Dr. Hwu is a 2018 candidate for SITC Vice President. Learn more about his candidacy here. Voting for the 2018 SITC Election takes place June 14–28, 2018.

1. What initially excited or intrigued you about the cancer immunotherapy field to choose this as your career focus?

When we get a viral infection, we can get very sick, but almost always fully recover. This powerful ability of the immune system to naturally cure viral illnesses has always intrigued me and encouraged me that applying this system against cancer could be impactful. In addition, the non-specificity and toxicity of current cancer therapies, such as chemotherapies, have always seemed unpalatable to me.  T-cells have the ability to distinguish normal peptides from mutated cancer-associated peptides that differ in merely one amino acid. This ability can enable anti-cancer therapies that have high efficacy and low toxicity. Even though immunotherapies in the early days were quite toxic, recent advances have allowed us to get closer to this dream of efficacious therapies without much toxicity. I routinely now have patients who travel to Europe and other distant places on vacation in between their outpatient treatments of immunotherapy. 

2. What advice would you share to an early career scientist contemplating a career in cancer immunotherapy?

Go for it!!  This is an exciting field.  I somewhat envy young investigators entering the field now. We know so much more than we knew when I was starting out, such as many of the immunoregulatory mechanisms of the body, and now have such great techniques like CyTOF and single cell RNA-seq to rapidly answer questions. Be curious, focused, and resilient. Many young investigators are intimidated by challenges with obtaining research funding. But there are in fact many more sources of funding now than traditionally in academia in years past. There is so much potential for us to make a great impact in cancer care, and we need as many talented young minds working on this as possible. Finally, don’t let anyone tell you something is impossible. In the early days, there were only a few of us who believed in immunotherapy and it is gratifying to see how many “converts” we have now.

3. What are three of the biggest hurdles facing researchers in the field, and how do you think they can be solved?

1. Moving immunotherapy responses beyond the common “immunogenic” tumor types.  In my opinion, this is largely due to the lack of sufficient CD8+ T-cells recognizing these cancers, i.e., lack of T-cell priming. This can potentially be solved using cancer vaccines, T-cell therapy and intratumoral immunomodulation, which are all very exciting and promising approaches.
2. Insufficient numbers of young investigators entering the field. Because of the challenges of funding, as well as the lack of enthusiasm for immunotherapy for many years in the past, there is a large deficit of talented, trained immunotherapy investigators. While this is starting to correct itself naturally, we need to move forward with urgency to train additional basic, translational and clinical investigators so we can fulfill the promise of immunotherapy to help the many cancer patients in need of better treatments.
3. Scalability with current approaches. Many of the most exciting current approaches towards immunotherapy, such as T-cell therapy and personalized vaccines, may have challenges with scaling treatments to the population in need in an affordable fashion.  There are many financial pressures on our current health care system, and biologists, engineers, politicians, and the business community must work together to bring these exciting therapies to the many people who need them.

4. What area of research has you most excited for the future of the field, and why?

I am most excited about the many ways we can prime the immune system to induce larger numbers of T-cells able to recognize cancers, many of which are considered “non-immunogenic.” While much of the field has focused on the release of immune checkpoint blockade, this will be ineffective if there is insufficient numbers of specific T-cells recognizing the cancer to begin with. Cancer vaccines, T-cell therapy, and intratumoral immunomodulation (for example, with TLR or STING agonists) are all very exciting areas with much promise. Combining these approaches in a rational way with other immunotherapies and targeted therapies also has much potential.