AACR19 Preview: CRI Scientists Showcase the Future of Immunotherapy

Cancer immunotherapy has become the hottest and most exciting area of cancer research today, with unprecedented investment in research and drug development from biotech, pharma, academic institutions, and nonprofit organizations producing record numbers of FDA approvals across multiple tumor types. On March 29, more than 20,000 scientists, clinicians, and others in the oncology space from around the world will gather in Atlanta, Georgia, for the 2019 Annual Meeting of the American Association for Cancer Research, where the latest data in this fast-moving field will be shared and discussed over the course of four days of plenary talks, oral abstract presentations, and poster sessions.

This year’s conference comes on the heels of the Nobel Foundation’s announcement in October last year that two immunologists—James P. Allison, PhD, director of the Cancer Research Institute (CRI) Scientific Advisory Council, and Tasuku Honjo, MD, PhD—would receive the 2018 Nobel Prize in Physiology or Medicine for their foundational breakthroughs in cancer immunotherapy.

As the Nobel nod made clear, immunotherapy’s value in the clinic is now beyond doubt. However, there are still a number of challenges that need to be addressed in order to maximize its therapeutic potential for patients. Which immunotherapies work best for which cancer types? Which biomarkers might be most useful in helping doctors determine the best treatment course for a particular person? Which immunotherapy combinations might work best together in order to extend immunotherapy’s benefits to more patients?

To that end, AACR19’s offerings—and the several dozen CRI scientists whose work will be featured at the conference—will cover a wide scope of both basic research and clinical investigation that seeks to provide answers to some of these questions as well as open up exciting new avenues for the development of novel and improved immune-based strategies.

In all, the work of 82 CRI scientists will be highlighted in more than 75 talks and 100 posters at AACR19. Below are some of the most exciting CRI-related presentations we’ll be watching closely.

Cornelis J. M. Melief, MD, PhD, a former CRI grantee who also currently serves on the CRI Scientific Advisory Council (SAC), will receive the 2019 AACR-CRI Lloyd J. Old Award in Cancer Immunology, in recognition of his innovative contributions to the field. In particular, Melief made many advances in the area of cancer vaccines, including some with CRI support. During the opening clinical trials plenary session, Melief will discuss a trial in which HPV-targeting vaccines, in combination with chemotherapy, were used treat patients with advanced cervical cancer. Melief is currently the emeritus professor of tumor immunology at the Leiden University Medical Center, the chairman of the Scientific Advisory Board of Translational Oncology at the University Medical Center of Johannes Gutenberg University, and the chief scientific officer at ISA Pharmaceuticals.

Also during the opening clinical trials plenary sessions, there will be an update on a CRI-funded pancreatic cancer trial being led by Robert H. Vonderheide, MD, DPhil, a CRI SAC member and the director of the University of Pennsylvania’s Abramson Cancer Center. This trial’s strategy, which involves four drugs including two immunotherapies targeting the PD-1 and CD40 pathways along with chemotherapy, is being explored as a first-line treatment for patients with metastatic pancreatic cancer, an extremely difficult-to-treat cancer that has received significant public attention with the recent announcement of Jeopardy! host Alex Trebek’s diagnosis with this disease and his resolve to overcome it.

A session on Sunday will focus on CRI-funded work from a phase I trial in which mesothelin-targeting CAR T cells were delivered regionally into patients with malignant pleural disease. This work is led by CRI-SU2C Dream Team member Michel Sadelain, MD, PhD, who directs the Center for Cell Engineering at Memorial Sloan Kettering Cancer. Sadelain, who will discuss the mechanisms that enable CAR T cell resistance in another talk, is also a member of CRI’s Clinical Accelerator Leadership.

Hyungseok Seo, PhD, a current CRI-Donald J. Gogel Postdoctoral Fellow at the La Jolla Institute for Allergy and Immunology, will highlight research into factors that might be able to help overcome CAR T cell dysfunction in solid tumors. This work is being led by Anjana Rao, PhD, a CRI SAC member who also serves as Seo’s fellowship sponsor and who was previously a CRI-funded fellow and investigator herself. Work led by Rao and involving Seo that examined other factors that influence CAR T cell activity will be the focus of an additional talk as well.

Gregory F. Sonnenberg, PhD, a current CRI-Thompson Family Foundation CLIP Investigator at Weill Cornell Medicine, will give a talk focusing on the complex environment of the intestinal tract and how various factors—including the trillions of bacteria that reside there—interact with and influence the activity of the immune system. In another talk, CRI SAC member Giorgio Trinchieri, MD, will discuss our current understanding of how these bacteria—which comprise part of the microbiome—fit into cancer immunotherapy strategies. Trinchieri is the director of the Cancer and Inflammation Program as well as the head of the Cancer Immunobiology Section at the National Cancer Institute.

Two separate talks will focus on B cells in the context of cancer immunotherapy. The first talk, which involves CRI SAC member Patrick Hwu, MD, the head of the division of cancer medicine and the chair of the Departments of Melanoma and Sarcoma Oncology at the University of Texas MD Anderson Cancer Center, will discuss the crucial role B cells play in immune responses after PD-1 checkpoint immunotherapy. The other talk will highlight the importance of B cells as well as tertiary lymphoid structures, and involves Allison, the 2018 Nobel laureate, as well as his MD Anderson colleague, fellow CRI-SU2C Dream Team member, and wife Padmanee Sharma, MD, PhD, and former CRI CLIP Investigator Nir Hacohen, PhD, of the Broad Institute of MIT and Harvard. Sharma is also currently leading a CRI-funded trial.

Robert D. Schreiber, PhD, an associate director of the CRI SAC whose lab at Washington University in St. Louis has been funded by CRI for much of the last twenty years, is chairing a session focusing on the complexities that arise from cancer’s ability to evolve and adapt over time. Schreiber will also give his own talk discussing the molecular basis for this immunoediting. During the session chaired by Schreiber, Sharma will be exploring the mechanisms behind resistance and response to checkpoint immunotherapy, whereas the University of California, Los Angeles’ Antoni Ribas, MD, PhD, a member of CRI’s Clinical Accelerator Leadership and the CRI-SU2C Dream Team, and the 2018 AACR-CRI Lloyd J. Old Award recipient, will cover combination immunotherapy strategies with the potential to overcome resistance to PD-1 immunotherapy.

Stephen J. Kron, PhD, a current CRI CLIP Investigator at the University of Chicago, will be exploring strategies that seek to shut off cancer’s “fountain of youth” by targeting tumor metabolism and disrupting their ability to repair themselves.

Work involving current CRI-Hearst Foundations fellow Susan Klaeger, PhD, and Nir Hacohen, PhD, her colleague at the Broad Institute, will be featured in a talk looking at novel ways to identify mutated tumor proteins that could be targeted with vaccines.

We can’t wait to cover the action on the ground in Atlanta and keep you updated on the most exciting news coming out of the conference. Be sure to follow our blog for daily recaps from AACR19!

Photo by Joey Kyber on Unsplash