The Promise of Immuno-oncology in Bladder Cancer

In the pursuit of advancing cancer treatment, immuno-oncology emerges as a promising therapeutic avenue. This blog delves into the importance of identifying antigens in developing targeted cancer therapies.

Immuno-oncology represents a pioneering shift in cancer therapeutics, harnessing the immune system to target tumors. This innovative approach not only offers personalized treatment regimens attuned to individual biology but may also ensure durable responses with fewer side effects than traditional treatments.¹ The potential to improve treatment outcomes using strategic FDA-approved immunotherapy combinations signifies a revolutionary advancement in cancer therapy.

Bladder cancer presents formidable challenges, with 573,000 cases in 2020 alone.² Its high recurrence necessitates continuous monitoring and often multiple therapeutic interventions. Treatments for bladder cancers can be highly invasive, ranging from transurethral resections to radical cystectomies,³ which can affect quality of life. In addition, side effects of treatments can be profound, underscoring the need for novel innovative therapeutic approaches and early detection strategies.

Within the evolving landscape of oncological care, the emergence of immunotherapy signifies a promising solution to addressing these challenges. Immunotherapy drugs, atezolizumab and pembrolizumab, have already demonstrated their potential for advanced urothelial carcinoma.⁴ In 2023, the FDA approved a novel immunotherapy combination: enfortumab vedotin-ejfv with pembrolizumab, positioned as a pivotal treatment for patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-based chemotherapy.⁵

The identification of bladder cancer-specific antigens remains crucial, underscoring the significance of advancing immune-centric therapies to ameliorate the prognosis and quality of life for patients.

By machine-reading the literature, Causaly uncovered over 4,000 genes and proteins reported to affect bladder cancer, Figure 1. Approximately half of these were shown to affect disease progression. Refining further revealed around 90 antigens associated with the progression of bladder cancer. The KIT protein (also known as CD117) was found to have the most compelling evidence in human trials.

CD117, which serves as an antigen, plays an important role in hematopoiesis, melanogenesis, mast cell development and stem cell maintenance.⁶ This protein is expressed in various cancers, from aggressive tumors to resistant tumors, often utilized as an indicator or poor patient survival.⁷

CD117 may show promise as a therapeutic target for bladder cancer. In a prospective clinical study, CD117 was detected in 38% of non-muscle-invasive bladder cancer cases, and the overall recurrence and progression rates correlated with CD117 overexpression.⁸ Interestingly, as tumors progressed from non-muscle invasive to muscle-invasive, CD117 expression was downregulated.⁸

Given its significant association with bladder cancer progression, CD117 presents itself as an intriguing antigen target for immuno-oncology interventions in bladder cancer.

Immuno-oncology represents a transformative approach in cancer care, leveraging the body’s immune defenses against tumors. With bladder cancer affecting numerous individuals globally, the identification of specific antigens like CD117 offers promising avenues for targeted therapies. As research progresses, the potential of  immuno-oncology treatments holds the promise to revolutionize bladder cancer treatment and enhance patient outcomes.