Activity of Broad-Spectrum T Cells as Treatment for AdV, EBV, CMV, BKV, and HHV6 Infections after HSCT

Abstract

It remains difficult to treat the multiplicity of distinct viral infections that afflict immunocompromised patients. Adoptive transfer of virus-specific T-cells (VSTs) can be safe and effective, but such cells have been complex to prepare and limited in anti-viral range. We now demonstrate the feasibility and clinical utility of rapidly-generated single-culture VSTs that recognize 12 immunogenic antigens from 5 viruses (Epstein-Barr virus, adenovirus, cytomegalovirus, BK virus, and Human Herpesvirus 6) that frequently cause disease in immunocompromised patients. When administered to 11 recipients of allogeneic transplants, 8 of whom had up to 4 active infections with the targeted viruses, these VSTs proved safe in all subjects and produced an overall 94% virological and clinical response rate that was sustained long-term.

Human herpesvirus-6 encephalitis after allogeneic hematopoietic cell transplantation: What we do and do not know

“…[85][86][87] Adoptive transfer of anti-HHV-6 T cells may effectively reduce the clinical manifestations of HHV-6 encephalitis or prevent HHV-6 diseases in the future.…”

Immunotherapy against cancer-related viruses

“…These studies have shown that even peripheral blood mononuclear cells (PBMCs) could be pulsed with peptides in the presence of cytokines to rapidly expand EB-VSTs, eliminating the need to make DCs. The cells manufactured using these accelerated and simplified strategies appear to be clinically effective [59], and the substantial reduction in time, complexity and cost has enabled the study of this approach in multi-national trials in lymphoma and NPC [55].…”

“…These viruses are classified into highrisk and low-risk groups according to the propensity for malignant progression of the lesions that they cause. Persistent infection of high-risk subtypes, such as HPV- 16,18,31,33,35,39,45,51,52,56,58,59, or 66, has long been known to predispose to the development of cervical cancer [108] and is also associated with carcinomas of the oropharynx and anogenital region. HPV infects basal epithelial cells where viral genomes are persistently maintained as low-copy number episomes [4].…”

Recent advances in T‐cell immunotherapy for haematological malignancies

“…With the availability of overlapping peptide libraries spanning individual EBV antigens, several groups have shortened the process and shown that rapidly expanded EBV-specific T-cells induce similar response rates. (Papadopoulou et al 2014a) (Icheva et al 2013) An alternative strategy to obtain rapidly available EBV-specific T-cells is to use banked “third-party” products derived from healthy donors. This approach has been tested in the clinic in patients with EBV-associated post transplant lymphoma with response rates of 60–80%.…”

“…The infusions were well tolerated and, on further analysis, a distinguishing characteristic between responders and non-responders was the induction of post-infusion epitope spreading to the non-viral lymphoma antigens MAGEA4, Survivin, and PRAME. (Bollard et al 2014) The success of autologous EBV-CTL therapy prompted several groups to explore more rapid generation methods(Ngo et al 2014, Papadopoulou et al 2014a), as well as “off-the-shelf” strategies using healthy donor-derived T-cells for EBV+ lymphomas. (Vickers et al 2014)…”