AACR 2023 Recap: CRI Scientists Tackle the Frontiers of Cancer Immunotherapy

More than any conference yet, the 2023 annual meeting of the American Association for Cancer Research (AACR 2023) highlighted just how far cancer immunotherapy has progressed. As the event revealed, Cancer Research Institute (CRI) scientists have been crucial to this progress and continue to advance the frontiers of this field to places few thought possible even as recently as last decade.

Perhaps the most exciting story out of AACR 2023 was a breakthrough involving personalized mRNA vaccines that target patient-specific neoantigens.

In a phase 2 trial for patients who underwent surgical resection for their high-risk melanoma, combining a personalized vaccine with PD-1 checkpoint immunotherapy reduced the risk of recurrence or death by 44%. Importantly, these benefits were observed regardless of how many mutations one’s tumor possessed. Typically, with checkpoint immunotherapy alone, tumors with more mutations are more likely to respond to treatment.

Whereas traditional cancer vaccines sought to stimulate immunity against tumor-associated targets that are often shared by healthy tissues, “more recent cancer vaccine approaches have focused on targeting neoantigens originated from individual tumor mutations, which are unique to cancer cells,” according to Jeffrey Weber, MD, PhD, of NYU Langone Health, who presented the data during the conference’s opening clinical trials plenary session.

“This study is extraordinarily important, because it gives hope that this novel strategy will provide clinical benefit,” added Dr. Weber.

While this vaccine directly leverages the ability of patients’ immune system to launch precise and powerful responses against their tumors, most research presented during the conference acknowledged the importance of immunology with respect to understanding the fundamentals of cancer biology. It’s become indisputable that the immune system plays a role in the genesis, development, and progression of cancer. And in many cases, like with the vaccine, the immune system must be accounted for in order to provide patients with optimal care for their individual disease.

T cells have earned much of the glory with respect to the success of immunotherapy, and rightly so. AACR 2023 showcased novel approaches to empower these specialized cancer-killing immune cells even further. Beyond T cells, the field has increasingly come to realize the importance of a variety of other factors, as was made clear by the latest update of the global Immuno-Oncology Landscape Analysis published in Nature Reviews Drug Discovery by the Cancer Research Institute (CRI) Anna-Maria Kellen Clinical Accelerator. Chief among these factors are the myeloid cells that dictate the immune nature of the tumor microenvironment and determine whether immune anti-tumor responses will be enhanced or suppressed.

Technology is also playing an increasingly important role in cancer care. By improving our ability to dissect the complexity of the cancer ecosystem — and all the cells, molecules, and pathways involved — novel tools are helping improve doctors’ diagnostic and prognostic capabilities. This enables the creation of more effective immune-based treatments for all types of cancer.

The amount of potentially transformative research and breakthroughs at AACR 2023 was substantial, as were the impacts of CRI physicians and scientists. To distill some of the most important findings that were made possible with CRI support, we spoke with four CRI-funded scientists who presented their work at the conference in several key areas.

Dr. Elsa Anagnostou on ctDNA and the Genomic Landscape of Checkpoint Immunotherapy

Valsamo ‘Elsa’ Anagnostou, MD, PhD, is a CRI Anna-Maria Kellen Clinical Accelerator Investigator at Johns Hopkins University School of Medicine who is currently leading the CRI-funded phase 2 trial “Study of Molecular Response Adaptive Immuno-Chemotherapy in Patients With NSCLC.” The goal of this trial is to evaluate whether blood tests that measure circulating tumor DNA (ctDNA) can help doctors more easily and reliably detect patient treatment responses compared to traditional radiographic scans.

Dr. Christopher Klebanoff on Neoantigen-Targeting Cell Therapies

Christopher A. Klebanoff, MD, is a CRI CLIP Investigator at Memorial Sloan Kettering Cancer Center who is studying the natural T cell response to ‘public’ neo-antigens in cancer patients to reverse engineer and create therapies from the T cells that recognize and attack these cancer-specific targets. Dr. Klebanoff also sponsors Lauren B. Banks, PhD, a CRI-Bristol Myers Squibb Postdoctoral Fellow in his lab, who is exploring a similar strategy to develop cell therapies for sarcoma, a rare family of tumors that arise from the body’s connective tissues and are typically resistant to current checkpoint immunotherapies.

Dr. Malay Haldar on the Impact of Myeloid Cells within Tumors

Malay Haldar, MD, PhD, is a CRI Lloyd J. Old STAR at the University of Pennsylvania who is mining the mysteries of myeloid cells, like macrophages and dendritic cells, that act as generals that orchestrate immune responses against tumors. By defining that factors that influence their behavior, and thus the effectiveness and anti-cancer immune responses, he hopes to identify strategies through which these cells can be manipulated to promote more effective tumor elimination.

Dr. Ido Amit on Technology to Decode the Complexity of the Tumor Microenvironment

Ido Amit, PhD, is a CRI Technology Impact Investigator at the Weizmann Institute of Science in Israel, who is developing a suite of technologies to help us crack the code of the cancer ecosystem. Specifically, he is mapping the molecular crosstalk of specific cell-cell interactions and the dynamics of these signaling events during different stages of tumor progression.

These four CRI scientists represent just some of the many exciting areas of innovation in cancer immunology and immunotherapy space that we saw at AACR 2023. With experts from all disciplines spreading the latest advances in cancer immunology among each other, there was a palpable and rejuvenating sense of progress on display. This will hopefully accelerate discovery from the next wave of laboratory experiments and clinical trials, ultimately leading to more effective cancer treatments and even a world immune to cancer.