Overcoming challenges for personalized cancer vaccines

Ilona Baraniak and Aleksandra Nevmerzhitskaya | Senior consultant and vaccine development specialist & Consultant and cancer immunology specialist

Advances in the field of personalized cancer vaccines create potential for more targeted, less toxic treatments for patients.

While many new cancer treatments have been developed in recent years, patients endure severe side effects due to the toxic nature of therapies and the indiscriminate ways in which they target cells. Personalized cancer vaccines, by virtue of being more targeted, are expected to make treatment far more tolerable for patients.

The benefit of personalized vaccines is that they stimulate the T cells to recognize only the cancer cells and kill them. All the other healthy cells in the body should stay untouched. As noted in a Nature paper, personalized cancer vaccines predicated on neoantigens can elicit tumor-specific T-cell responses, averting off-target damage to non-malignant tissue.

In addition, as the global population continues to age, cancer is expected to become an even greater burden and, while treatments are improving, many types of cancers can’t be addressed by generalized therapies. Personalized cancer vaccines could, in future, address many of these cancers.

Nevertheless, there are many challenges for developers of these vaccines to overcome.

Since these products are patient-specific, various tests that are typically performed during the manufacture and product release can’t be carried out. While it’s not possible to perform certain batch release tests, there are always alternatives that can provide a high level of confidence that the product is safe and will work in the way predicted. The limitations on testing mean companies need to be more targeted in their approach, for example, focusing stability testing on extreme conditions.

Other challenging issues are the ability to manufacture the product fast enough to deliver to the patient in the time required. That’s because personalized vaccines require a unique manufacturing and supply chain process, starting with the tumor biopsy from the patient to manufacturing the vaccine and then to getting that vaccine back to the patient. Another issue is the ability to identify neoantigen epitopes (neoepitopes) that will bind to MHC class II and I molecules, which is key to mount and sustain immune responses.

From a regulatory perspective, the global landscape continues to evolve alongside the science. Guidances are yet to be developed and even when the regulators do release guidelines, the highly dynamic nature of the field means they are likely to be constantly updated. In addition, lack of harmonization globally means approaches accepted by some agencies may not be accepted by others. That can make it difficult to navigate and requires companies to be ready to negotiate with the authorities on a product-by-product and region-by-region basis.

Preparing early

While there are a growing number of companies developing personalized cancer vaccines, most are in preclinical or early clinical trials, or at best phase 2 trials. It makes sense, however, to prepare approaches and strategies in order to address challenges as early as possible.

During the clinical trial design, it’s important to find the right population and it makes sense to look at combining these with the right immune checkpoint inhibitors or other therapeutic interventions, since studies show the combination can elevate efficacy.

As the science and regulations continue to evolve, it’s important to have ongoing dialogue with the agencies, and develop smart solutions built upon knowledge of different types of precision medicines.

The complex nature of the science means companies will need to adopt some type of informatics tool to identify the right target for the vaccine to ensure a good clinical response. Technology advances, such as artificial intelligence and machine learning tools, can be hugely beneficial in this regard.

Much remains unknown about personalized cancer vaccines and inevitably new hurdles as well as breakthroughs will arise.  Timely interaction and transparency during the communication with the authorities will help the innovators to improve their chance of success. Such early engagement will assist regulators as they create new guidelines addressing the manufacturing challenges while embracing the innovations.

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