NEW IMMUNOLOGY AVENUES

The use of immune checkpoint inhibitors has expanded across oncology, but these are not the only types of immuno-oncology treatments under investigation. The Education Session “Beyond Checkpoint Blockade: An Update on Engineered T-Cell Therapy and Neoantigen Vaccine Application” will bring experts together for a discussion on some of the other immuno-oncologic avenues that could help improve patient outcomes. The session will be held on June 3 and chaired by Gianpietro Dotti, MD, PhD, of the University of North Carolina, Chapel Hill, and UNC Lineberger Comprehensive Cancer Center. He will begin with a discussion of CAR T-cell therapy and its expanding clinical indications.

There are now two CAR T-cell therapies approved by the U.S. Food and Drug Administration for certain patients with acute lymphoblastic leukemia and lymphoma; Dr. Dotti will focus on what other settings this promising therapy might expand to.

TILs and Neoantigen Vaccines

Stephanie L. Goff, MD, of the National Cancer Institute Center for Cancer Research, will speak about tumor-infiltrating lymphocyte (TIL) therapy.

“Lymphocytes that grow and thrive within a tumor can help us identify how a patient’s immune system has learned to ‘see’ their cancer,” Dr. Goff said. “We can use that knowledge to build highly personalized experimental cell treatments.”

She added that by engaging a specific repertoire of lymphocytes, this type of adoptive cell therapy should have fewer autoimmune toxicities than can occur with immune checkpoint blockade. The strategy, she said, is feasible regardless of a cancer’s histology, and so far, responses have been observed in malignancies, including melanoma, cholangiocarcinoma, colon cancer, and breast cancer.

“For common epithelial cancers, the adoptive transfer of TILs has a meaningful, if small, clinical response rate and allows us to study immune mechanisms of human tumor recognition and relapse in vivo,” Dr. Goff said. “We hope to improve on our clinical response rate by cultivating a more enriched TIL population or genetically engineering cells with the same ability to recognize mutations present in the tumor.”

It is important for clinicians and patients to embrace clinical trials earlier in a patient’s metastatic disease course to move the field forward quickly, she said. “As with most clinical trial research, the stronger our patients, the stronger our science can be,” Dr. Goff added.

Neoantigen vaccines are another promising avenue of immuno-oncology research, which Patrick A. Ott, MD, PhD, of the Dana-Farber Cancer Institute, will discuss. Neoantigens arising from somatic mutations provide tumor-specific targets for a personalized cancer vaccine; trials with these vaccines have begun to demonstrate promising results either alone or in combination with immune checkpoint blockade. Trials are ongoing in several cancers, including pancreatic, triple-negative breast, renal cell, hepatocellular, urothelial, and others.

Variations on T-Cell Receptor Therapy

Cassian Yee, MD, of The University of Texas MD Anderson Cancer Center, will discuss what he described as a “recent renaissance” in T-cell therapy. There are efforts to expand the CAR/T-cell receptor (TCR)–engineered therapy, which has been shown to be effective in B-cell malignancies and multiple myeloma, toward other types of malignancy.

“The goal of ‘off-the-shelf’ therapy is possible with this approach; however, it would be naive to assume translation from CAR [T-cell] therapy of liquid tumors to solid tumor malignancies will be straightforward,” Dr. Yee said. “There is limited flexibility to engineered T cells because this requires a priori knowledge of the TCR or antibody single-chain variable fragment, and stringent regulatory approval.”

Another major focus of his talk will be endogenous T-cell therapy (ETC), which involves T cells sourced from a patient’s peripheral blood. “The opportunity to select from a wider TCR repertoire and generate memory CD4⁺ and CD8⁺ T cells with defined specificity has advantages over other modalities,” Dr. Yee said. “Enabling technologies to isolate very rare antigen-specific T cells from peripheral blood and expand to several billion has been achieved in treatment of many solid tumors.”

He said there have been very few serious toxicities associated with ETC therapy, which has no absolute requirement for high-dose lymphodepletion or high-dose interleukin-2 and can be considered an outpatient therapy.

“Targets evaluated by ETC allow investigators to more fully vet them in a clinical trial before undertaking the more laborious process of engineering and seeking approval for use of engineered TCRs for these targets,” he added. “Strategies to streamline this approach will broaden its appeal.”

Dr. Yee said that he will also look forward to and anticipates an increase in the use of combination therapy approaches and an interest in the potential of allogeneic T-cell therapy.