A vaccine targeting mutant IDH1 in newly diagnosed glioma

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Mutated isocitrate dehydrogenase 1 (IDH1) is identified as a distinct molecular subtype of diffuse glioma, with the IDH1(R132H) mutation being the most prevalent. This mutation presents a unique neoepitope on MHC class II, enabling the development of an IDH1(R132H)-specific peptide vaccine (IDH1-vac) that elicits targeted T helper cell responses against IDH1(R132H)+ tumors. A phase I trial involving 33 patients with newly diagnosed grade 3 and 4 IDH1(R132H)+ astrocytomas demonstrated the vaccine's potential. The discussion also highlights the emerging field of cancer vaccines, noting that while the concept is relatively new, it is part of the broader cancer immunotherapy landscape. Current immunotherapy approaches include checkpoint inhibitors and CAR-T therapy, which leverage the immune system to combat cancer.
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Mutated isocitrate dehydrogenase 1 (IDH1) defines a molecularly distinct subtype of diffuse glioma1,2,3. The most common IDH1 mutation in gliomas affects codon 132 and encodes IDH1(R132H), which harbours a shared clonal neoepitope that is presented on major histocompatibility complex (MHC) class II4,5. An IDH1(R132H)-specific peptide vaccine (IDH1-vac) induces specific therapeutic T helper cell responses that are effective against IDH1(R132H)+ tumours in syngeneic MHC-humanized mice4,6,7,8. Here we describe a multicentre, single-arm, open-label, first-in-humans phase I trial that we carried out in 33 patients with newly diagnosed World Health Organization grade 3 and 4 IDH1(R132H)+ astrocytomas (Neurooncology Working Group of the German Cancer Society trial 16 (NOA16), ClinicalTrials.gov identifier NCT02454634).

Are cancer vaccines a super new thing? I have not heard of a vaccine for cancer before.
https://www.nature.com/articles/s41586-021-03363-z
 
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Greg Bernhardt said:
Are cancer vaccines a super new thing? I have not heard of a vaccine for cancer before.
https://www.nature.com/articles/s41586-021-03363-z

The idea of creating a vaccine to prime the immune system to attack cancer is fairly new, though many groups are working on this idea. For example, here's a PF thread from 3 years ago discussing research related to anti-cancer vaccines: https://www.physicsforums.com/threads/new-cancer-research-at-stanford.938605/

Here's a more general article on the topic: https://www.cancerresearch.org/immunotherapy/treatment-types/cancer-vaccines

The idea of anti-cancer vaccines is related to the broader idea of cancer immunotherapy, which is one of the big new ideas in cancer research. Basically, the goal of cancer immunotherapy is to use the body's own immune system to fight cancer. Current cancer immunotherapy drugs being used in the clinic include checkpoint inhibitor therapy (which helps get around defenses that cancer cells use to hide from the immune system; this idea was awarded the Nobel Prize in Medicine in 2018) and CAR-T therapy (which involves engineering immune cells to better be able to fight cancer cells).
 
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