Cancer Vaccines FAQ

To explore how cancer vaccines work, which cancers they could target, and the challenges facing their development, we return to a two-part The Medicine Maker feature from 2024, in which five industry experts discussed the state of the field.

How do vaccines prevent and/or treat cancer?

Jens Bjørheim, Chief Medical Officer of Ultimovacs: “As a normal cell develops into cancer cells and eventually tumors, the cancer cells become increasingly different from their healthy counterparts, representing an opportunity for the immune system to detect and kill the cancer cells. The most well-described differences that are potential targets for the immune system are genetic mutations and the presence of proteins that are otherwise repressed. A cancer vaccine can be produced using molecules that mimic these changes observed in the tumor. There are many ways (platforms) that can be used to generate such molecules that the T cells can react to. Common platforms include peptides or DNA and RNA vaccines that encode for sequences of amino acids alike those of the abnormal tumor. Specific T cells then react to these molecules, and start to proliferate searching for cancer cells that have the same mutated or abnormal proteins.”

Nicolas Poirier, Chief Executive Officer of OSE Immunotherapeutics: “Essentially, cancer vaccines re-educate our immune system by providing the tumor antigens that the immune system should recognize but currently tolerates. Cancer vaccines can hence form new T-cell ‘troops’ that can patrol and detect cancer cells expressing those tumor antigens. After surgery, when cancer vaccines are used as an adjuvant, the trained lymphocytes can detect remaining tumor cells and eliminate them to avoid tumor recurrence. In metastatic and advanced cancer patients, T lymphocytes have died or are highly exhausted, in particular after immunotherapy resistance. The cancer vaccine helps form new and fresh immune cells.”

Justin Duckworth, Chief Executive Officer of Transimmune: “Therapeutic vaccination of cancer is one of the most ambitious goals in medicine. It seeks to cure cancer in the same way our natural immunity protects us for much of our lives against nascent malignant cells, by tapping into the extraordinary specificity and firepower of the immune network. Everyone’s cancer is unique, making ‘one-size-fits-all’ therapies challenging and crude by design. Cancer vaccines can be either generically targeted or personalized to a specific patient. The former can be expected to be less precise but with economic benefits.”

Which cancers can be targeted with vaccines – and why?

Bjørheim: “In theory, vaccines can target all types of cancers. The fundamental principle is the immune system’s capacity to recognize and fight abnormal cellular changes. As long as the immune system can recognize mutated or abnormal proteins, vaccines can potentially be a viable treatment modality for any form of the disease.”

Duckworth: “There is much debate over which cancers represent the most promising targets for successful vaccination. Two lenses often used to view a tumor’s attractiveness for vaccination are mutational load and the tumor microenvironment. For mutational load, the greater the load, the more likely it is that the immune network can spot abnormalities on the surface of the tumor cell and target it for destruction. In the tumor locality, a loss of systemic and/or local T cell integrity increases the difficulty of creating a successful vaccine. T cell suppression in the tumor microenvironment and lymphoid organs is addressed by checkpoint inhibitors, though imprecisely because they target all T cells, regardless of their specificity, thus resulting in autoimmune side effects.”

What are the big challenges facing cancer vaccine development?

Myriam Mendila, Chief Development Officer of CureVac: “A significant challenge is deciding which tumor antigens to target. Some patients have 8,000 tumor-specific antigens; others have just 100 or less. We need to develop smart selection algorithms based on specific criteria, supported by AI, to identify and prioritize the antigens that really matter.

“A second challenge is the ability to deliver vaccines quickly. This can go down two routes – the provision of pre-prepared or so-called ‘off-the-shelf’ cancer vaccines based on tumor antigens known to be shared across different cancer indications or fully personalized vaccines based on a patient’s individual tumor genomic profile. The former is faster as relevant antigens can be anticipated while the latter takes longer due to mandatory steps, such as taking a biopsy, sequencing the tumor tissue of a given patient, designing and producing an individualized vaccine, and getting the vaccine to the patient. This can take around 6 weeks to 3 months. We need to find solutions to produce the personalized cancer vaccine in particular in the fastest way as patients with cancer usually can’t wait for their treatment.”

Poirier: “Identification of the right antigens is not the same at the early versus late stage – because tumors evolve and resistance mechanisms vary. This means we need to diagnose more patients, especially those with solid tumors, at an earlier stage and to prepare ‘off-the-shelf’ vaccines composed by several shared tumor-associated antigens across tumor development to treat quickly patients and avoid tumor escape from one or two antigen mutations.”

Paul-Peter Tak, Chief Executive Officer of Candel Therapeutics: “Engineering the right agent to engage the immune system in the right way to yield durable antitumor responses is a challenge. Approaches designed to stimulate the anti-tumoral response ex vivo against multiple antigens are elegant, but implementation is complicated by relatively high costs, extended timelines, and its use is limited to specialized centers. mRNA vaccination is simpler in terms of implementation, but provides different challenges because it typically focuses the immune response against a single antigen.”

Bjørheim: “Though checkpoint inhibitors have demonstrated substantial efficacy, they do not work for all patients. In some indications, such as malignant melanoma and non-small cell lung cancer (NSCLC), a higher proportion of patients respond compared with other indications like mesothelioma and head and neck cancer. Additionally, some cancers, such as prostate and pancreatic cancers, have yet to establish checkpoint inhibitors as standard of care.

“Because of the mutual interaction between checkpoint inhibitors on one side and the immune system or vaccines on the other, patients who do not respond to checkpoint inhibitors are likely to see little or no effect from a therapeutic cancer vaccine. To broaden the application of vaccines, we need new checkpoint inhibitors or drugs that make the tumor more accessible for the immune system.”

The phase III INTerpath-001 announcement provides new context for several issues raised by the contributors, including the use of cancer vaccines after surgery, their combination with checkpoint inhibitors, and the need for evidence from large randomized trials. Questions concerning antigen selection, production times, cost, and access remain relevant as personalized cancer vaccines move through late-stage development.

Read the full discussion in Cancer Vaccines: Activate the Immunosoldiers – Part I and Part II.