Advances in virus-specific T-cell therapy for polyomavirus infections: A comprehensive review.

Polyomaviruses are a group of small, non-enveloped, double-stranded DNA viruses that can infect various hosts, including humans. BKPyV causes conditions such as human polyomavirus-associated nephropathy (HPyVAN), human polyomavirus-associated haemorrhagic cystitis (HPyVHC), and human polyomavirus-associated urothelial cancer (HPyVUC). JC polyomavirus (JCPyV), on the other hand, is the causative agent of progressive multifocal leukoencephalopathy (PML), a severe demyelinating disease of the central nervous system. PML primarily affects immunocompromised individuals, including those with HIV, recipients of certain immunosuppressive therapies, and transplant patients. The treatment options for HPyV infections have been limited, but recent developments in virus-specific T cell (VST) therapy have shown promise. Although VST therapy has shown potential in treating both BKPyV and JCPyV infections, several challenges remain. These include the time-consuming and costly preparation of VSTs, the need for sophisticated production facilities, and uncertainties regarding the optimal cell type and infusion frequency. To the best of our knowledge, 85 patients with haemorrhagic cystitis, 27 patients with BKPyV viremia, 2 patients with BKPyV nephritis, 14 patients with haemorrhagic cystitis and BKPyV viremia, and 32 patients with PML have been treated with VST in the literature. The overall response results were 82 complete response, 33 partial response, 35 no response, and 10 no-outcome-reported. This review underscores the importance of VST therapy as a promising treatment approach for polyomavirus infections, emphasising the need for continued research and clinical trials to refine and expand this innovative immunotherapeutic strategy.