Cancer and the Advent of Immunotherapy
Cancer is a leading cause of death in the developed world, and has historically been treated with surgery, radiation therapy, chemotherapy and hormone therapy, which use nonspecific mechanisms to attempt to remove or to kill cancer cells. More recently, therapies have focused on harnessing the immune system to fight cancer. In particular, the pioneering work of one of our founders, Dr. James Allison, has resulted in a new class of immunotherapy known as checkpoint inhibitors. By counteracting signals from cancer cells that suppress immune responses, checkpoint inhibitors allow the immune system to reengage and attack these cells.
Checkpoint inhibitors have demonstrated particularly potent efficacy in cancers with higher mutational load, which is characteristic of cancers such as melanoma and lung cancer. However, even in these tumor types, the majority of patients do not respond to checkpoint inhibitors. In addition, there are many tumor types that have lower rates of mutation where checkpoint inhibitors do not yet play a significant role. We believe that neoantigen-targeted therapies may precisely direct the immune system to improve patient outcomes across both checkpoint-responsive and unresponsive disease.
Mutations and the Immune System
Genetic mutations are the hallmark of cancer, and mutant proteins encoded by these mutations can result in uncontrolled division and proliferation of abnormally functioning cells. These same mutated proteins can also be processed into shorter fragments called peptides and presented as immune signals on the surface of cancer cells, called neoantigens. The immune system can recognize these neoantigens as foreign, just as it would recognize foreign peptides from bacteria or viruses.
The genetic mutations from any given tumor are often unique to each patient, making up a mutational fingerprint. At Neon Therapeutics, we work to understand the unique mutational fingerprint from every patient and tumor, identify how these mutations could result in important neoantigen immune targets, and develop neoantigen-targeted therapies specific to each mutation and patient.
Neoantigens: Cancer’s Untapped Vulnerability
Neoantigen-targeted therapies seek to direct the immune system towards neoantigen targets by enhancing existing immune responses and generating new immune responses. By directing the immune system towards these targets, we believe that neoantigen-targeted therapies will offer a new level of patient and tumor specificity in the field of cancer immunotherapy, driving a strong risk-benefit profile to dramatically improve patient outcomes.
Neoantigen-targeted therapies fundamentally differ from prior attempts to provide the immune system with a target, which focused primarily on tumor-associated antigens that, unlike neoantigens, are not specific to the tumor and are also found in normal cells. Those targets are subject to central and peripheral immune tolerance, leading to a dampened immune response.
We believe that neoantigen-targeted therapies confer a number of significant benefits over historic approaches targeting tumor-associated antigens, including:
- exclusive specificity to the tumor;
- broad immunogenicity;
- broad applicability across cancer types including those with both high and low tumor mutational burden;
- potential for use in frontline treatment settings; and
- being a key component of rational cancer treatment combinations.
Neon Therapeutics is proud that initial feasibility, safety, immunogenicity and clinical outcomes for a personal neoantigen vaccine in patients with adjuvant melanoma were published by founders of Neon Therapeutics in Nature in 2017.