The power of philanthropy in transforming cancer research

PICI Catalyzes Scientific Innovation

By Luis Felipe Campesato, PhD, and Roberta Zappasodi, PhD

Immunotherapy has revolutionized oncology treatment and has brought hope to many patients battling cancer—though many challenges still remain. Efforts aimed at better understanding the interactions between cancer and our immune system are urgently needed to improve the efficacy of immunotherapy for more tumor types.

To advance scientific research—a dynamic process which constantly challenges itself and its theories—we, as scientists, are highly dependent on interactions within our community. We can praise individuals for key contributions, but successes in science rarely come from lone achievements. They come through collaborative efforts.

“…successes in science rarely come from lone achievements. They come through collaborative efforts.”

Take, for instance, the groundbreaking laboratory findings in inhibitory immune checkpoints from immunologists Drs. James Allison and Tasuku Honjo, who received the 2018 Nobel Prize in Physiology and Medicine. These seminal discoveries have been implemented and translated into life-saving therapies as a result of partnerships between academia and industry^1,2. These successes are a testament to the impact of highly collaborative teamwork.

Bold philanthropic initiatives like the Parker Institute for Cancer Immunotherapy (PICI) are fostering this type of strategic collaboration by supporting innovative science to conquer cancer. PICI aims to rapidly bring new cancer immunotherapy treatments to patients through an unprecedented model that breaks through bureaucratic “red tape” in translating research findings to the clinic.

Memorial Sloan Kettering Cancer Center (MSK), one of the nation’s leading cancer centers that partner with PICI, has embraced this model, sharing expertise and data within PICI’s network. In turn, PICI facilitates cross-pollination and partnership among top academic and industry researchers across the nation, infuses MSK with expert resources such as informatics and biobanking capabilities to extract insights out of our research more efficiently, and provides access to state-of-the-art technology and funding for high-risk ideas.

Thanks to PICI, our lab at MSK—led by PICI director Dr. Jedd Wolchok and PICI investigator Dr. Taha Merghoub—gained cutting-edge equipment and resources for immune monitoring.

We now have access to a state-of-the-art multiplex tissue imaging system, with the ability to detect up to seven markers on tissue biopsies simultaneously, and a multiparameter flow cytometer, which allows us to detect up to 28 markers at once in blood and tissue samples from cancer patients.

These technologies greatly improve our capacity to investigate the dynamic interactions between cancer and the immune system. The high-throughput analyses are fostering our efforts towards discovering, for instance, new biomarkers of response to immunotherapy. And because these new technologies are not only open to our lab but the entire institution, they will ultimately have a broader impact on research at MSK.

As part of its strategy to accelerate the translation of treatments from bench to bedside, PICI also supports multi-center immunotherapy trials that originate from innovative ideas within its research network. Our lab was directly involved in the opening of PICI’s first clinical study (MAHLER), a Phase II trial which tested whether CTLA-4 blockade as a monotherapy or in combination with PD-1 blockade could benefit patients with anti-PD-1 refractory advanced melanoma (NCT02731729). More recently, our lab joined another PICI-sponsored trial that aims to shed light on mechanisms underlying response to immunotherapy in patients with difficult-to-treat solid tumors (NCT03651271).

On a personal note, PICI invests in talented early career scientists through highly competitive programs. One of us, Roberta Zappasodi, was a recipient of a Parker Scholar Award in 2017 and subsequently a Parker Bridge Scholar Award in 2019. Through the network and resources made available to our lab, she discovered a new subset of immunosuppressive T cells (4PD-1^hi T cells) that act as a potential biomarker for immune checkpoint blockade activity. The research was reported in Cancer Cell last year³. Such findings may advance our capacity to predict and improve response to immunotherapy. In Zappasodi’s words on her experience as a PICI member:

“I’ve been inspired by PICI both in and outside the lab. Through retreats and workshops facilitated by PICI, I was introduced to pioneers in cancer immunotherapy and fellow up-and-comers. This experience has exposed me to new science and broadened my thinking, which I brought back to the bench. Many of these researchers are now key collaborators on projects I’m working on today. One includes a study to identify blood-based biomarkers of response to PD-1 blockade in collaboration with Alexander Huang, a Parker Bridge Scholar at the University of Pennsylvania, and Lacey Padrón, director of informatics at PICI. This opportunity would not have arisen if not for the Parker Institute.

True to its mission, PICI has paved the way for other collaborative opportunities. I recently introduced PICI to another organization I am working with, TimIOs. This SITC initiative addresses a major hurdle in the field: to understand the molecular basis of response and resistance to PD-1 pathway blockade. As a result of our synergies, we convened major players across academia, pharma and biotech in a workshop to discuss how to improve translational data analysis, coordinated by PICI senior data scientist Danny Wells. PICI and TimIOs have now engaged in a consortium with academic players — the University of North Carolina at Chapel Hill and the Institute for Systems Biology — to accelerate our research toward a better understanding of immunotherapy response. We presented our initial results at the 2019 SITC Annual Meeting. We look forward to discovering new biomarkers guiding the development of rational and more effective combination immunotherapy programs.”

– Roberta Zappasodi

By cultivating a collaborative attitude in scientific research and removing many roadblocks cancer researchers often face, PICI promotes creative thinking that ultimately translates ideas into impactful discoveries. Core to the institute is developing and nurturing an interactive network of people who share the common mission to build knowledge that benefits patients’ lives. This is what makes PICI a unique catalyzer of scientific breakthroughs. After all, as John Lennon sang, a dream dreamt alone is just a dream. A dream dreamt together can become reality.

Luis Felipe Campesato, PhD, is a research associate in the Parker Institute for Cancer  Immunotherapy, and Ludwig Collaborative and Swim Across America Laboratory, Human Oncology & Pathogenesis Program at Memorial Sloan Kettering Cancer Center. He contributes to science magazines and blogs.

 Roberta Zappasodi, PhD, is a 2019 Parker Bridge Scholar and research associate in the Parker Institute for Cancer Immunotherapy, and Ludwig Collaborative and Swim Across America Laboratory, Human Oncology & Pathogenesis Program at Memorial Sloan Kettering Cancer Center. She is currently establishing her independent research team.

References

1. Wolchok, J. D. et al. Development of ipilimumab: a novel immunotherapeutic approach for the treatment of advanced melanoma. Annals of the New York Academy of Sciences 1291, 1-13, doi:10.1111/nyas.12180 (2013).
2. Chen, L. & Han, X. Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future. J Clin Invest 125, 3384-3391, doi:10.1172/JCI80011 (2015).
3. Zappasodi, R. et al. Non-conventional Inhibitory CD4(+)Foxp3(-)PD-1(hi) T Cells as a Biomarker of Immune Checkpoint Blockade Activity. Cancer Cell 33, 1017-1032 e1017, doi:10.1016/j.ccell.2018.05.009 (2018).