Beyond the Immune Checkpoint Blockade
The immunotherapy field is expanding beyond the immune checkpoint antibodies already approved (ipilimumab) and in late stages of development (nivolumab, MPDL3280A, and MK-3475). At a 1-day conference, the 4th Annual Cancer Immunotherapy: A Long Awaited Reality Conference, held at the New York Academy of Medicine, biotechnology companies that focus on cancer immunotherapy presented their platforms and agents in development.
Several companies are focusing on boosting T-cell activity against tumors by engineering human cells to produce antigens and adjuvants, which, like vaccines, can prime and modulate an immune response.
North Carolina–based Heat Biologics is developing fully human cytotoxic T-cell–specific adjuvants. The company’s platform is based on creating human allogeneic cell lines from primary tumor samples engineered to secrete the heat shock protein gp96, as well as a selected group of tumor-specific antigens. Gp96 has previously been shown to stimulate specific immunity to tumor peptides, modulating both the innate and adaptive immune system pathways. The company screens these types of cell lines, created from a spectrum of different tumors, to identify antigens shared among many patient samples.
Heat Biologics is currently developing its cell-based therapy to stimulate the immune systems of patients with tumor types that have thus far been less amicable to immunotherapy. A phase II clinical trial of HS-110, a cell therapy for advanced lung cancer, is being planned to test for the ability of the cell therapy to stimulate a T-cell response to multiple lung cancer antigens, facilitated by gp96. A phase I/II clinical trial of a similar cell therapy for bladder cancer is currently enrolling patients.
Massachusetts-based Agenus focuses on the discovery and testing of fully human antibodies. Specifically, they are currently focused on novel immune checkpoint antibodies and preclinical programs targeting numerous checkpoint molecules distinct from anti-PD1 and anti–CTLA-4 antibodies currently in the clinic. The program to discover and develop new checkpoint antibodies is in conjunction with Memorial Sloan-Kettering Cancer Center in New York City. Agenus has immune checkpoint modulator antibodies, such as GITR and OX40 agonists, as well as TIM-3 and LAG-3 antagonists, proteins that function in the stimulation of T-cells.
New Jersey–based PDS Biotechnology takes a non–cell-based approach. The company is working on synthetic and biodegradable lipid molecules that carry tumor antigens. According to PDS, these nanoparticles work as adjuvants, taken up by immune cells to prime T-cells for enhanced antigen uptake and processing. A phase I clinical trial is testing the concept in women with human papillomavirus (HPV)–positive cervical intraepithelial neoplasia.
If proven safe in early-stage trials, these agents are likely to all have potential as part of combination immunotherapies with either engineered T-cell approaches or immune checkpoint inhibitors.
The 4th Annual Cancer Immunotherapy: A Long Awaited Reality Conference at the New York Academy of Medicine in New York City was sponsored by MaidStone Life Sciences LLC.