Science

Marco Donia: Personalized Cancer Vaccines in Renal Cell Carcinoma – Phase I Study

Marco Donia/dff.dk

Feb 17, 2025, 08:07

Marco Donia: Personalized Cancer Vaccines in Renal Cell Carcinoma – Phase I Study

Marco Donia, Associate Professor in Clinical Oncology at the University of Copenhagen, shared an article by David A. Braun, et al. on LinkedIn:

“Personalized Cancer Vaccines in Renal Cell Carcinoma: Phase I Study.

Free access at Nature Magazine, David Braun et al., Feb 2025

Background:

Renal cell carcinoma (RCC) has low tumor mutational burden and a high recurrence risk after surgery, with limited success from current adjuvant therapies. Personalized cancer vaccines (PCVs) targeting tumor-specific neoantigens aim to train the immune system to attack tumors.

Key findings from this Phase I trial (NCT02950766):

9 patients with high-risk RCC received a personalized peptide-based neoantigen vaccine (+/- ipilimumab), targeting up to 20 patient-specific mutations (VHL, PBRM1, BAP1, KDM5C, PIK3CA).
All patients developed T-cell responses (primarily CD4+), including against RCC driver mutations.
At 40 months median follow-up, no patient had disease recurrence.
The vaccine was well tolerated.

How do Personalized Cancer Vaccines (PCVs) Differ?

Peptide vs. mRNA: Peptide-based vaccines (this study, NEO-PV-01, EVX-01) have demonstrated strong immune responses; mRNA-based vaccines (mRNA-4157) + pembrolizumab reduced melanoma recurrence in the KEYNOTE-942 trial (Phase 3 ongoing), more.
Computational strategies for antigen selection vary between research teams= Vaccine A (by team A) may target different neoantigens than Vaccine B (by team B), even in the same cancer type.
Adjuvants differ between vaccines, potentially influencing immune activation and response durability.

Open Questions:

Will larger trials confirm recurrence-free survival in RCC (and melanoma)?
Can PCVs boost clinical responses in metastatic disease?

Take-home messages:

Personalized cancer vaccines are already in Phase III for melanoma.
The absence of recurrence in this small RCC cohort is promising, and requires validation in larger trials.

A neoantigen vaccine generates antitumour immunity in renal cell carcinoma.

Authors: David A. Braun, et al.

Marco Donia: Personalized Cancer Vaccines in Renal Cell Carcinoma - Phase I Study

cancer clinical oncology David Braun fight against cancer Global fight against cancer Marco Donia mRNA Nature Magazine neoantigen vaccine OncoDaily Oncology pembrolizumab personalized cancer vaccines RCC renal cell carcinoma University of Copenhagen

In Memory of Alan Rickman and His Battle with Prostate and Pancreatic Cancer

New Paper Alert: Systemic management of advanced HCC: an increasingly complex game

AC-satoreotide got FDA Orphan Drug Designation status for SCLC and MCC

Oncologist Near Me – Nazik Hammad: A Leader in Cancer Care, Medical Education, and Health Equity

Garo Armen - A Bold Call to Action: Embracing Real-Time Innovation in Pediatric Cancer