Third-party cytomegalovirus-specific T cells improved survival in refractory cytomegalovirus viremia after hematopoietic transplant

Abstract

JWY common stock in Merck, Pfizer, and Amgen. RJO consultancy, research support and royalties Atara BiotherapeuticsThe IND and license to develop the Third Party CMV-CTL program was transferred to Atara Biotherapeutics in July 2015 and transferred back to MSKCC in July 2019. The data related to these studies is solely the responsibility of MSKCC Atara Biotherapeutics has no financial interest in and has not seen or reviewed this manuscript prior to submission.

Another tool against cytomegalovirus after allogeneic hematopoietic cell transplantation

“…The Prockop et al ( 12 ) results also point to potential opportunities for optimizing VSTs. None of the seven subjects treated with CMVpp65-VSTs specific for epitopes presented by HLA B35 responded to therapy, suggesting that these high-risk patients may need alternative strategies.…”

“…In this issue of the JCI , Prockop et al ( 12 ) present the combined clinical results of three separate phase I or II clinical trials that treated a total of 67 subjects with refractory CMV viremia or organ disease with the adoptive transfer of banked, third-party CMV pp65–sensitized virus-specific T cells (CMVpp65-VSTs). In contrast with donor-derived patient-specific VSTs, each third-party CMVpp65-VST line selected for infusion was (a) restricted by an HLA allele that was shared by the patient and the patient’s HCT donor and (b) shared at least two HLA alleles with the patient ( Figure 1 ).…”

“…In contrast with donor-derived patient-specific VSTs, each third-party CMVpp65-VST line selected for infusion was (a) restricted by an HLA allele that was shared by the patient and the patient’s HCT donor and (b) shared at least two HLA alleles with the patient ( Figure 1 ). Although Prockop et al ( 12 ) allowed for CMVpp65-VSTs to be administered after failure of one line of therapy, 19 out of 59 subjects had failed three lines of therapy (ganciclovir and/or valganciclovir, foscarnet, and cidofovir and/or brincidofovir), and 20 out of 59 patients had organ involvement and/or organ dysfunction due to CMV infection, indicating a heavily treated and high-risk population. Clinical responses were reported in 38 of 59 (64%) evaluable subjects.…”

“…Partial response was defined as a 2-log, or 100-fold, decrease in CMV viral load and resolution of clinical symptoms related to disease. Overall survival at six months was increased for responders to CMVpp65-VSTs compared with nonresponders (79% versus 29%, P < 0.001) ( 12 ).…”

“…Interestingly, serial chimerism analysis in a subset of patients showed that circulating CMVpp65-388–specific T cells after infusion could originate predominantly from the recipient, the stem cell donor, or from the third-party donor. Based on these results, the authors posited that long-term control of CMV in responders may not necessarily be directly from third-party CMVpp65-VSTs; the infused product may somehow stimulate T cells from the stem cell donor or residual recipient T cells to mount a durable anti-CMV response ( 12 ).…”