Cancer vaccines

Therapeutic vaccines could provide a transformative shot in the arm for cancer treatment.

After decades of slow progress, therapeutic vaccines that direct the immune system to attack tumours could soon become a fixture of cancer treatment.

Treatments that could train the immune system to identify and destroy cancer cells are on the way.

Brody and colleagues discuss the current status and potential of cancer vaccines, highlighting challenges and opportunities to advance promising candidates to the clinic.

A phase I clinical trial of an adjuvant personalized mRNA neoantigen vaccine, autogene cevumeran, in patients with pancreatic ductal carcinoma demonstrates that the vaccine can induce T cell activity that may correlate with delayed recurrence of disease.

In situ vaccine recruits and activates cross-presenting dendritic cells and augments PD1 blockade efficacy in patients with indolent non-Hodgkin’s lymphoma.

RNA vaccines have been associated with high reactogenicity. Mellman and colleagues demonstrate that lipid-formulated RNA vaccines trigger IL-1 production and inflammation in humans but this pathway is dampened in mice.

In the ongoing phase 1/2 BNT211-01 trial, CLDN6-specific chimeric antigen receptor (CAR)-T cells given with or without CARVac, a CAR-T cell-amplifying RNA vaccine, were well-tolerated and exhibited encouraging clinical activity in patients with relapsed or refractory CLDN6-positive solid tumors, with the highest response rate in patients with germ cell tumors.

Results of an exploratory interim analysis from a phase I trial show that an RNA vaccine targeted towards four melanoma-associated antigens produces durable objective responses in patients with melanoma that are accompanied by strong CD4⁺ and CD8⁺ T-cell immunity.