Relapse after HSCT 2021 | The GVL effect of VSTs
Catherine Bollard, MBChB, MD, FRACP, FRCPA, Children’s National Health System, Washington, DC, talks on the graft-versus-leukemia (GVL) effect of off-the-shelf viral-specific T-cells (VSTs). Whilst numerous studies have demonstrated that VST therapy is not associated with graft-versus-host disease (GvHD), one case of GVL without GvHD has been observed in a patient receiving VSTs following bone marrow transplant (BMT). Prof. Bollard reports that this anti-leukemic effect was caused by the marked expansion of VSTs in the peripheral blood at the time of leukemia clearance. Larger studies investigating this effect will be conducted in the future. This interview took place at the 2021 Relapse After HSCT² Workshop in New York, NY.
Transcript (edited for clarity)
It is very interesting that off-the-shelf VSTs have been used so effectively in terms of even a one-on-six match. We can see efficacy ranges between 50 to over 90% for some really refractory viral infections in our bone marrow transplant patient population. And we think that the efficacy is that good, especially when you know you have a shared virus-specific T-cell activity through a shared HLA allele...
It is very interesting that off-the-shelf VSTs have been used so effectively in terms of even a one-on-six match. We can see efficacy ranges between 50 to over 90% for some really refractory viral infections in our bone marrow transplant patient population. And we think that the efficacy is that good, especially when you know you have a shared virus-specific T-cell activity through a shared HLA allele. But I often get asked, well, how come you don’t see graft-versus-host disease? And one reason we hypothesize is because we actually do have rigorous release criteria showing that the third-party VSTs don’t kill completely HLA-mismatched antigen-presenting cells in cytotoxicity assays.
So, that being said, while we’ve published on more than 200 infusions showing limited to no graft-versus-host disease, we did publish a few years ago on an interesting case of graft-versus-leukemia effect without graph-versus-host disease. So, this was a child who had received VSTs as prophylaxis after bone marrow transplant and a routine bone marrow at the time actually came back showing that the patient had detectable leukemia in their bone marrow. And we didn’t do anything, intervene, because the patient had only just received the VSTs. So, we repeated the bone marrow a few weeks later, and it was completely normal. And ultimately, the patient relapsed several months later in the testes, which is, of course, immune privilege site.
But it was intriguing to us to look deeper into whether the VSTs had a role in the clearance of the leukemia from the bone marrow. And sure enough, we saw a marked expansion of the virus specific T-cells in the peripheral blood at the time of leukemia clearance. And we actually saw cross-reactivity with tumor-associated antigens in the VST product, meaning that there were T-cells present in that VST product that were cross-reactive with tumor-associated antigens expressed by the patient’s leukemia cells.
So, I think it is interesting to know that there is this potential for VSTs to have a graft-versus-leukemia effect, but this obviously has to be evaluated in much larger randomized controlled trials. And really, I think that’s where I think the field will be going as now this technology is broadening into pharma interest with recent companies, including Atara and AlloVir investigating these sorts of products in the transplant setting.
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Disclosures
Catherine Bollard, MBChB, MD, FRACP, FRCPA, is the Co-founder and scientific advisory board member of Catamaran Bio and Mana Therapeutics, is a board member of Cabaletta Bio, owns stock in Neximmune, Repertoire Immune Medicines and DSMB- SOBI; and participates in advisory boards for Pfizer, BMS and Roche on an ad hoc basis.
