Therapies targeting cancer's escape mechanisms show promise

Dr. Zocca, with over 20 years in the biotechnology field, has made significant contributions to translational and clinical immune oncology. She has founded and co-founded multiple biotech spinouts, leading to the development of investigational immunotherapies for various cancers. Dr. Zocca earned her Ph.D. in tumor immunology and a Master of Science in biochemistry. Her doctoral studies were conducted at the Institute of Medical Microbiology and Immunology, University of Copenhagen, and the National Cancer Institute (NCI) in Bethesda, Maryland, USA.

For patients battling advanced or rapidly progressing cancers, new treatments are urgently needed. Current therapies for common cancers like melanoma often present a dilemma: choosing between strong efficacy with severe side effects or moderate efficacy with moderate toxicity. Dr. Zocca has been driven by the promise of therapies designed to dismantle cancer cells' defenses, allowing the immune system to combat the disease more effectively.

In 2014, Dr. Zocca established IO Biotech, aiming to enhance patient outcomes by developing innovative therapeutic vaccines. These vaccines are designed to transform the tumor microenvironment, making it hostile to cancer cells. Cancer treatments have historically struggled due to the disease's ability to shield itself from the immune system. Some treatments target specific proteins overexpressed in the tumor microenvironment, allowing the body's immune defenses to attack cancer cells more effectively. However, tumor cells also produce proteins that prevent T cells from killing them. Immune checkpoint inhibitors (ICIs) have managed to make cancer cells more susceptible to T cells by blocking these proteins, but resistance to these therapies remains a challenge. Overcoming this resistance could significantly improve cancer treatment efficacy.

A promising strategy involves not only targeting and destroying tumor cells but also enhancing the mechanisms that make ICIs effective by addressing the cells that contribute to immune system resistance. Some cancer vaccines target neoantigens, which are proteins with unique mutations found only in tumor cells. These vaccines require customization for each patient. Other vaccines aim to activate T cell immunity against proteins commonly overexpressed by certain cancers. This method could allow for the production of ready-to-use therapies that can be manufactured more efficiently, delivered faster, and applied to a broader patient base. These vaccines might also target immune-suppressive antigens expressed by non-tumor cells in the tumor microenvironment, potentially improving therapy efficacy. By targeting both tumor and non-tumor cells, these therapies aim to activate the immune response to destroy both cell types. The goal is to shift the tumor microenvironment from being protective of cancer cells to being hostile to them.

At IO Biotech, the T-win platform utilizes a repertoire of molecules to create off-the-shelf drug candidates that target antigens enabling cancers to evade the immune system. Their leading candidate, IO102-IO103, targets cells producing IDO and PDL-1, antigens commonly found in the tumor microenvironments of melanoma patients. A Phase 1/2 trial combined IO102-IO103 with nivolumab for metastatic melanoma, resulting in a high objective response rate (ORR) of 80%, with 50% of patients achieving a complete response and a median progression-free survival of nearly 26 months. Importantly, the safety and tolerability of the therapy were comparable to ICI therapies targeting the PD-1 antigen alone, with no added systemic toxicity from IO102-IO103. An ongoing Phase 3 clinical trial may lead to the therapy’s availability in the United States by 2025.

The success of targeting antigens in the tumor microenvironment could extend hope beyond melanoma patients. If IO102-IO103 continues to demonstrate safety and efficacy without additional systemic toxicity, it could offer a new treatment option for melanoma and potentially other challenging cancers. This approach could also impact other therapeutic areas that have not seen new treatments in recent times.