Company News: Towards a Best Practice Approach in Cancer Immunotherapy: Cancer Vaccines Gain Momentum
– Review in The Journal of Clinical Investigation points the way forward for therapeutic cancer vaccines
ISA Pharmaceuticals B.V., a clinical-stage immunotherapy company focusing on rationally designed immunotherapeutics against cancer and persistent viral infections, today announced the publication of a comprehensive scientific review of therapeutic cancer vaccines, outlining the best available strategies for successfully eradicating tumors with immunotherapy. The article, which was published in The Journal of Clinical Investigation, was authored by a group of scientists from Leiden University Medical Center (LUMC); lead author is Cornelis Melief, professor at LUMC and CSO of ISA Pharmaceuticals. The researchers point out that considerable progress has been made with therapeutic cancer vaccines, resulting in prolonged patient survival, but also conclude that most strategies have not resulted in objective, durable tumor regressions.
Looking at numerous studies, the authors have identified crucial success factors for better clinical outcome in cancer immunotherapy by vaccination:
- Sufficient antigen concentration in dendritic cells,
- an effective route of administration,
- the use of an adjuvant that can stimulate dendritic cells,
- the choice of combination therapy and, above all,
- selection of the right antigen.
“With few exceptions, the design of many cancer vaccines has fallen short of important parameters for success,” said Prof. Melief. “As an example, it is now clear that cancer vaccines need co-treatment and cannot be expected to work as a monotherapy. In peptide-based immunotherapies, we now know that only concentrated antigen sources such as DNA, RNA or synthetic long peptides can raise robust CD4+ and CD8+ T cell responses. But it is also very clear today that the best results can only be achieved by choosing antigens that are unique to the cancer, thereby avoiding central immunological tolerance.”
He noted that many immunotherapies for non-viral cancers have targeted antigens that are shared by tumor cells and normal cells, albeit with different levels of expression. However, the T cells induced by these antigens rely on the T cell repertoire left after the induction of central immune tolerance in the thymus. Therefore, the available repertoire is depleted of high-avidity T cells, resulting in suboptimal immune responses.
“This is different in cancers induced by viruses,” added Ronald Loggers, CEO of ISA Pharmaceuticals. “We are therefore seeing impressive outcomes with our lead candidate ISA101, which targets cancers induced by human papillomavirus infection. In the light of recent findings, reviewed in the JCI article, we will also focus on neo-antigens, i.e. novel antigens arising from mutations, for the treatment of non-viral cancers. Like the viral antigens, the neo-antigens are not subject to central immunological tolerance of a thymic nature, and therefore vaccination against neo-antigens fosters T cells with strong cancer killing capacity. As they are patient-specific, our synthetic long peptide (SLP®) approach is well suited for the design of personalized immunotherapies against neo-antigens.”
He added that the benefits of the SLP® platform include robust CD4+ and CD8+ T cell response induction, high specificity, absent toxicity, lasting efficacy and short time-to-patient.
Loggers concluded: “The validity of our SLP® platform is expected to be further strengthened by early 2016, when immune response data and early clinical observations will be evaluated from the dose-finding phase of ISA’s Phase 1/2 CervISA trial. In this study, late-stage HPV16 positive cervical cancer patients are treated with ISA101 in combination with standard of care chemotherapy. Recruitment is on target and scheduled to be completed during the fourth quarter of 2015.”
 Melief CJM, van Hall T, Arens R, Ossendorp F, van der Burg SH. Therapeutic Cancer Vaccines. J Clin Invest. 2015;125(8). doi:10.1172/JCI80009