Using Vaccines to Bolster Immunotherapy Responses in Kidney Cancer

Vaccines are currently being tested in their potential to improve immunotherapy responses for patients with renal cell carcinoma.
While vaccines have had difficulty in the treatment landscape of renal cell carcinoma (RCC), they are now being tested to possibly improve response rates with checkpoint inhibitors, says Tian Zhang, M.D.
Zhang notes that over the past 10 years, three viral vectors that test vaccines in kidney cancer — TG4010, MVA-5T4 and IMA901 — have not succeeded in clinical trials. “My question is, ‘Are vaccines a lost cause or are they a way forward?’ Certainly, there have been several lost causes that we've seen thus far, but as we get better at designing vaccines, hopefully this is a step forward in improving immunotherapy for kidney cancer,” says Zhang.

In an interview with CURE, Zhang, a medical instructor in the Department of Medicine, Duke University School of Medicine, discusses the challenges associated with vaccine development in kidney cancer and the hope that vaccines can still be the answer to improving the response rates with anti–PD-1/PD-L1 treatment in RCC.

Could you provide an overview of vaccines in the treatment of RCC?

There is an excitement around checkpoint inhibitors in RCC. There is a question of whether there is a way to improve the response rate we see in checkpoint inhibitors with vaccines, due to its immunogenicity in RCC.

There have been three negative trials thus far of viral vectors that test vaccines in kidney cancer, transgene TG4010, MVA-5T4 and IMA901. These have, unfortunately, spanned the last decade in testing so it has been very hard to think about which tumor antigens are the optimal ones to target, which should we present to T cells to activate them, and which particular tumor antigens we should go after.

The transgene virus vector presents a specific tumor antigen and there is one from the IMA901 that presents about 10 different tumor antigens, but they are all prespecified and off-the-shelf. There is one from Argos that is a dendritic cell vaccine, which takes both dendritic cells as well as tumor RNA from patients directly and integrates those, so that, when infused into the patient, the dendritic cells will activate the T cells based on the patient’s repertoire of tumor antigens. That one showed pretty promising results in a phase 2 study and is currently undergoing a phase 3 in combination with Sutent (sunitinib) in the first-line setting.

I think the challenge in vaccine development is selecting those tumor antigens versus personalizing and targeting them to the patient. Secondly, there is an ever-rising bar of first-line treatment for metastatic RCC and so that first-line therapy and the comparison arm with certainty change in the ongoing trials and the trials we design in the future.

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