Daniel Peeper: Therapeutic approaches combined with PD1 axis blockade to provide synergistic clinical benefit

Daniel Peeper, Head of the Division of Molecular Oncology and Immunology at the Netherlands Cancer Institute, shared a post on LinkedIn:

“Happy to share a new poster published by Nature Reviews Cancer and Nature Reviews Immunology, put together by Daniela Thommen and myself. It illustrates therapeutic approaches that are combined with PD1 axis blockade to provide cooperative or synergistic clinical benefit.

Technological advances have increased our mechanistic understanding of cancer–immune interactions and enabled the discovery of treatments that promote anti-tumour immunity, with ICB of the PD1–PDL1 interaction being a prime example.

However, for most advanced cancers, the benefit of single-agent therapy is limited by several mechanisms, including factors within the TME that curtail effective immune responses.

Therefore, many clinical trials are ongoing to combine PD1 axis blockade with other therapies, most often conventional chemotherapy or radiotherapy. On this poster, we highlight combinations with new therapeutic targets and modalities.

Importantly, the number of potential treatment combinations is far greater than the patients available for clinical trials, resulting in missed possibilities, clinical failure, unnecessary side effects, inadequate patient recruitment and financial setbacks.

It is crucial, therefore, that therapies are combined in a more rational manner, translating fundamental biological insights and mechanistic understanding.

The justification for treatment combinations is to establish cooperative or synergistic clinical benefits, based on the simultaneous targeting of different signalling pathways in cancer cells, immune cells or other cells of the TME.

The response to ICB can fail in several ways, for example, at the level of effector T cells (CD4, CD8 and gd T cells); suppression of CD8 T cells by other immune cells such as Treg cells or neutrophils and macrophages; lack of tumour recognition by T cells; or T cell-suppressive factors in the TME.

We have illustrated several approaches in each of these four categories that can be combined with PD1 axis blockade, including innovative preclinical concepts, clinical trials, as well as FDA-approved treatments.”

Source: Daniel Peeper/LinkedIn