A New Age for Vaccine Therapy in Renal Cell Carcinoma

Abstract

Over the past several years, the dominant paradigm in drug development for metastatic renal cell carcinoma (mRCC) has been to more selectively and potently target moieties such as the vascular endothelial growth factor receptor (VEGFR). The effectiveness of this strategy appears to be nearing a plateau, however, underscoring the need for novel approaches. Vaccine-based therapies represent one such approach. Several distinct vaccines are currently being examined in mRCC, each utilizing a distinct mechanism of action. For instance, the autologous dendritic cell vaccine AGS-003 utilizes patient-specific antigens derived from primary tumor tissue. In contrast, the poxvirus vaccine TG4010 produces an antigenic response to MUC1, a cell surface glycoprotein that reduces cell-cell interactions and thereby precludes contact inhibition. Other vaccines elicit a response to a broader spectrum of antigens – for instance, the vaccine IMA901 is based on 9 tumor-associated peptides identified from a novel biotechnology platform combining mass spectroscopy, microarray analysis of RNA expression, and immunogenicity assays. Herein, the current status of vaccine-based therapies for mRCC is described in detail. Furthermore, challenges to clinical implementation (e.g., cost, optimal pairing with targeted agents, appropriate sequencing) are presented.

Checkpoint inhibitors and other novel immunotherapies for advanced renal cell carcinoma

“…Vaccine strategies in cancer immunology can differ in the antigen used, the manufacturing mode, and the adjuvant used 85,86 . Attempts at treatment with modified virus vaccines targeting a single tumour antigen have been disappointing.…”

Emerging Role for Novel Immunotherapy Agents in Metastatic Renal Cell Carcinoma: From Bench to Bedside

“…Phase I and II studies of the multipeptide mRCC vaccine IMA901 have demonstrated encouraging overall survival in the subset of patients who also received a single dose of cyclophosphamide in addition to the vaccine. [97][98] A randomized phase III study of IMA901, cyclophosphamide, and GM-CSF plus sunitinib versus sunitinib alone as fırst-line therapy for patients with metastatic RCC is currently ongoing. 99 AGS-003 is a personalized, autologous dendritic cell vaccine that has been examined in phase II clinical trials in combination with sunitinib.…”

Therapeutic Vaccines for Genitourinary Malignancies

“…The field of genitourinary malignancies has been a showcase for therapeutic cancer vaccine success since the application of intravesicular Bacillus Calmette-Guerin (BCG) for bladder cancer in the 1970s [ 5 ] and enjoyed a renaissance in 2010 with the US Food and Drug Administration (FDA) approval of sipuleucel-T for prostate cancer [ 6 ]. Several vaccine strategies have emerged, such as autologous or allogeneic whole-tumor vaccines, DNA vaccines, use of viral vectors, and peptides as immunostimulatory adjuvants [ 7 , 8 ]. In addition to their elegant mechanism of action, vaccine strategies are clinically valuable for having a low adverse event profile.…”