ASCO 2025 | How splicing neoantigens expands tumor landscape for immunotherapy
Darwin Kwok, PhD, University of California, San Francisco, CA, comments on the potential of splicing neoantigen targeting to complement existing immunotherapy strategies. Dr Kwok suggests that splicing neoantigen targeting could enhance the specificity and potency of immunotherapies by selectively targeting tumor-specific splicing variants. However, he also highlights the need to overcome technical hurdles, including the development of efficient and scalable methods for identifying and isolating these variants, as well as the optimization of delivery systems to ensure effective tumor penetration. This interview took place during the 2025 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.
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Transcript
Thank you for the question. So, I think splicing neoantigen targeting is a very exciting area of research, and it has the potential to complement existing immunotherapy strategies in several ways. One way is that splicing neoantigens are tumor-specific and can be presented by the tumor cells in a way that’s not dependent on the tumor’s mutational burden. This means that splicing neoantigen targeting can potentially be effective in tumors that are cold or have low mutational burden, which is a limitation of some existing immunotherapies...
Thank you for the question. So, I think splicing neoantigen targeting is a very exciting area of research, and it has the potential to complement existing immunotherapy strategies in several ways. One way is that splicing neoantigens are tumor-specific and can be presented by the tumor cells in a way that’s not dependent on the tumor’s mutational burden. This means that splicing neoantigen targeting can potentially be effective in tumors that are cold or have low mutational burden, which is a limitation of some existing immunotherapies. Another way that splicing neoantigen targeting can complement existing immunotherapies is by targeting a different type of antigen. Most existing immunotherapies target somatic mutations or viral antigens, whereas splicing neoantigens are derived from aberrant splicing events that occur in cancer cells. This means that splicing neoantigen targeting can potentially target a different subset of cancer cells that are not targeted by existing immunotherapies. In terms of technical hurdles, one of the main challenges is identifying the splicing neoantigens that are presented by the tumor cells. This requires a combination of bioinformatic and experimental approaches to identify the splicing events that occur in cancer cells and to validate that these events are immunogenic. Another challenge is developing effective strategies for delivering the splicing neoantigens to the immune system. This could involve using viral vectors or other delivery methods to express the splicing neoantigens in a way that stimulates an immune response. Finally, there’s also the challenge of understanding how to combine splicing neoantigen targeting with existing immunotherapies. This could involve combining splicing neoantigen targeting with checkpoint inhibitors or other immunotherapies to enhance the anti-tumor response. Overall, I think splicing neoantigen targeting is a very promising area of research, and it has the potential to complement existing immunotherapies in several ways. However, there are still several technical hurdles that need to be overcome before it can be implemented in the clinic.
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