Researchers led by Ludwig Harvard’s Kai Wucherpfennig reported in a May Nature paper the design and preclinical evaluation in mice and primates of a new type of cancer vaccine that could be broadly effective against cancers. Vaccines elicit immune reactions to antigens, so they often need to be personalized to be effective against cancer due to the enormous variability of both the randomly mutated peptides presented as “neoantigens” and the major histocompatibility complex molecules that present them to T cells. Complicating the task further, cancers can evolve mechanisms to thwart peptide presentation. The new vaccine targets the MICA and MICB (MICA/B) stress proteins expressed on the surface of human cancer cells in response to DNA damage. MICA/B binding can activate natural killer (NK) and T cells through the NKG2D receptor, but cancer cells snip the telltale proteins off their surface to evade such responses. Antibodies elicited by the new vaccine interfere with that snipping, leaving MICA/B intact to stimulate NK and T cell activation. Kai and his colleagues showed that their vaccine is safe and effective, elicits an enhanced assault on cancer by both NK and T cells, and works even against tumors with a resistance mutation in the MHC class I antigen presentation pathway. Notably, it prevents the resurgence of metastases in animal models after the surgical removal of aggressive primary tumors.
Read the study: A vaccine targeting resistant tumours by dual T cell plus NK cell attack, Nature, 2022 May 25 Epub
This article appeared in the September 2022 issue of Ludwig Link. Click here to download a PDF (1 MB).