Therapies designed to dismantle cancer’s escape mechanisms show promise for patients

20 May 2024
www.biopharmadive.com
VaccineClinical ResultImmunotherapyPhase 3
Dr. Zocca brings more than 20 years of experience in the biotechnology field and has founded and co-founded several biotech spinouts. Her focus on translational and clinical immune oncology has led to the development of important investigational immunotherapies for a variety of cancer types. Dr. Zocca holds a Ph.D. in tumor immunology and a Master of Science in biochemistry. She received her Ph.D. from the Institute of Medical Microbiology and Immunology, University of Copenhagen, and the NIH, National Cancer Institute (NCI)Cancer Institute (NCI), Bethesda, Maryland, USA.
For many patients with advanced stage or rapidly progressing cancers, new treatments can’t come fast enough. Current therapies for common cancers such as melanoma often force patients and their healthcare providers to choose between strong efficacy with potentially serious side effects, or moderate efficacy and moderate toxicity. Throughout my career in academia and industry, I’ve been captivated by the potential of therapies that could help strip down the defenses used by cancer cells to keep the immune system at bay.
Aiming to transform the lives of cancer patients by improving patient outcomes, I founded IO Biotech in 2014 to develop novel therapeutic vaccines that seek to alter the tumor microenvironment to make it hostile to cancer cells.
Challenges with current approaches to cancer treatment
Cancer has always been difficult to treat because it defends itself so effectively against the body’s immune system. Treatments that single out specific proteins that are overexpressed in the tumor microenvironment can target tumor cells directly while also enabling the body’s own immune defenses to attack and kill those cells more effectively on their own.
However, tumor cells and other cells in the tumor microenvironment express proteins that block T cells from killing cancer cells. The advent of immune checkpoint inhibitors (ICIs) made cancer cells more vulnerable to T cells by disrupting the proteins that block immune response.
Unfortunately, cancer’s resistance to these therapies can limit the efficacy of this approach. Finding ways to dismantle cancer’s escape mechanisms and counter that resistance could help improve the efficacy of cancer treatments.
A promising approach to dismantling cancer’s defenses
In addition to targeting and destroying tumor cells themselves, cancer vaccines also have the potential to improve the mechanism that makes ICIs work by targeting the cells that generate immune system resistance.
Some vaccines target neoantigens—proteins with unique mutations expressed only by tumor cells. These vaccines are highly targeted, but they must be customized for each patient.
Other vaccines are designed to activate T cell immunity against proteins commonly overexpressed by specific cancers. This approach may enable biotech companies to produce off-the-shelf therapies that can be manufactured more easily, delivered to patients more quickly, and applied more broadly across patient populations. These vaccines may also be able to target immune-suppressive antigens expressed by non-tumor cells in the tumor microenvironment, potentially improving the therapies’ efficacy. Targeting both tumor and non-tumor cells is intended to effectively jump-start the body’s immune response, activating it to help destroy both types of cells on its own. Ideally, the therapy transforms the tumor microenvironment from protective toward cancer cells to hostile to them.
The latter approach shows considerable promise. At IO Biotech, our T-winÒ platform leverages a catalog of molecules to generate off-the-shelf drug candidates targeting antigens that allow cancers to avoid attack by the body’s immune system.
Our lead candidate, IO102-IO103, targets cells that produce IDO and PDL-1, two antigens commonly overexpressed in melanoma patients’ tumor microenvironments. A Phase 1/2 trial, which combined IO102-IO103 with nivolumab in metastatic melanoma, produced a high objective response rate (ORR) of 80%, with 50% of patients reaching a complete response and a median progression-free survival of nearly 26 months.1 Importantly, the overall safety and tolerability data were comparable to those of ICI therapies targeting the PD-1 antigen alone, with IO102-IO103 not adding any systemic toxicity.2 Results from an ongoing Phase 3 clinical trial could bring the therapy to patients in the United States as early as 2025.
What’s next for cancer vaccines
Targeting antigens in the tumor microenvironment could deliver much-needed hope to patients beyond the growing population of people with melanoma. If IO102-IO103 clinical results continue to demonstrate the combination of safety and efficacy we have seen so far without adding systemic toxicity, it could provide another therapeutic option for melanoma patients. Provided we can identify the right antigens to target, this approach could also offer hope to patients with a variety of difficult-to-treat cancers. It also could have an impact in other therapeutic areas that have not benefited from new treatments in some time.
Sources:
1 Lorentzen et al, 2023
2 Kjeldsen et al, 2021
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