Immune-Modulating Cancer Vaccines: Transforming Treatment

Vaccines have revolutionized public health since their inception centuries ago, significantly reducing the prevalence of deadly infectious diseases and thereby extending life expectancy. In recent decades, the scientific community has explored the potential for vaccines to treat non-infectious diseases such as cancer. However, the outcomes of clinical trials have largely been underwhelming. Since 1990, only three cancer vaccines have received approval from the Food and Drug Administration (FDA).

Despite past setbacks, recent scientific advancements and encouraging preclinical study results have rejuvenated the field of cancer vaccine development. More than 350 clinical trials are currently underway, with oncologists and patients hopeful that the latest generation of cancer vaccines will demonstrate high efficacy and low toxicity.

Historically, one of the primary reasons for the failure of cancer vaccines was insufficient understanding of tumor biology and its interaction with the immune system. Tumors employ various mechanisms to evade immune detection, including manipulating the immune system to ignore the tumor. However, recent research has shown that these escape tactics can be counteracted at a molecular level.

One promising approach involves vaccines that train the immune system to recognize and destroy cancer cells. These vaccines can be either personalized or "off-the-shelf." Personalized vaccines are tailored to target specific antigens unique to an individual's tumor. This process involves extracting a tumor sample, identifying its unique antigens, and incorporating these antigens into a vaccine. Although effective, this method is time-intensive and may delay treatment.

Alternatively, off-the-shelf vaccines target common antigens found in many patients with a specific type of cancer. These vaccines are easier to produce and store, thus facilitating quicker treatment initiation.

A significant challenge in developing cancer vaccines is the tumor's ability to create an immune-suppressive microenvironment. Tumors can manipulate immune cells to inhibit the body's cancer-fighting capabilities, thereby promoting tumor growth and complicating treatment.

To overcome this, new treatments are being designed to reactivate the immune system's attack on cancer. A novel class of immune-modulating cancer vaccines aims to not only train the immune system to kill tumor cells but also to eliminate immune-suppressive cells within the tumor microenvironment.

These immune-modulating vaccines can initiate a therapeutic chain reaction. By transforming the tumor microenvironment from cancer-friendly to cancer-hostile, they enable immune system cells to attack the tumor more effectively. As tumor cells are destroyed, they release additional antigens, which further stimulate the immune response. This enhances the initial attack on the tumor, potentially prolonging its effectiveness and improving the efficacy of other immunotherapies.

At IO Biotech, our lead immune-modulating cancer vaccine candidate, IO102-IO103, targets cells expressing IDO and PD-L1. This dual targeting approach aims to combat both tumor cells and immune cells responsible for resistance mechanisms in cancer patients. In a Phase 1/2 clinical trial, IO102-IO103, when combined with an immune checkpoint inhibitor (ICI), showed promising results in patients with metastatic melanoma. The safety profile was comparable to that of ICI therapies targeting PD-1, without additional systemic toxicity. If ongoing Phase 3 trials are successful, this therapy could be available in the United States by 2025.

The development of vaccines that can overcome the immune-suppressive tumor microenvironment offers an exciting and promising treatment avenue. Producing off-the-shelf drug candidates could revolutionize cancer treatment and have broader applications for other difficult-to-treat diseases, bringing new hope to patients.