Pilot trial of K562/GM-CSF whole-cell vaccination in MDS patients

Abstract

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell malignancies. Currently, approved drugs are given with non-curative intent as the only known cure is allogeneic bone marrow transplantation, which relies on the donor's immune system driving an allogeneic effect. Previous efforts to harness the endogenous immune system have been less successful. We present the results of a pilot study of K562/GM-CSF (GVAX) whole-cell vaccination in MDS patients. The primary objective of safety was met as there were no serious adverse events. One patient had a decrease in transfusion requirements and another demonstrated hematologic improvement suggesting a signal for clinical activity. In vitro correlative studies indicated biological effects on immune cells following vaccination. Although only a pilot study, results are encouraging that an immunotherapeutic approach with a whole-cell vaccine may be feasible in MDS patients.

A human cell-based SARS-CoV-2 vaccine elicits potent neutralizing antibody responses and protects mice from SARS-CoV-2 challenge

“…We further showed the same regimen was effective in rhesus macaques as it was capable of inducing authentic neutralizing antibody to a level 3-fold higher than human convalescent sera, suggesting the possibility of successful translation to human clinical trials. K562-derived whole-cell vaccine approach has been previously explored for cancer treatment by engineering K562 to express immune-regulatory cytokines, and more recently tumor antigen [17][18][19]. Such exploration established the safety of inactivated K562-derived vaccine for human use.…”

“…K562-derived whole-cell vaccine approach has been previously explored for cancer treatment by engineering K562 to express immune-regulatory cytokines, and more recently tumour antigen [ 17–19 ]. Such exploration established the safety of inactivated K562-derived vaccine for human use.…”

“…Of importance, irradiation-mediated inactivation has been demonstrated to be sufficient for securing the biosafety of transfusion of K562 cells. Indeed, irradiated K562 cells expressing granulocyte-macrophage colonystimulating factor (GM-CSF) have been clinically assessed for treating myelodysplastic syndromes (MDS) and chronic myeloid leukemia (CML) patients, with noted hematologic improvements and no serious adverse events [17][18][19]. Accordingly, we engineered K562-S to stably express S-protein, namely K562-S, and subsequently study its efficacy after inactivation, either alone or in combination with different adjuvants, as vaccine against SARS-CoV-2 in preclinical animal models.…”

Whole tumor cell vaccines engineered to secrete GM‐CSF (GVAX)

“…A randomized study comparing K562 GVAX versus interferon plus GM‐CSF for patients failing to achieve molecular remission after tyrosine kinase therapy in CML has been initiated (NCT00363649). A smaller trial of K562 GVAX in MDS demonstrated safety and feasibility but no clear clinical responses 79 . In myeloma patients receiving lenalidomide, vaccination with allogeneic myeloma lines, K562/GM, and Prevnar‐13 converted eight of 15 myeloma patients from a near CR to a full CR with tumor‐specific immunity demonstrated 80 …”

Antiviral T-cell Biofactory platform for SARS-CoV-2

“…We determined the prophylactic and therapeutic effects of the IFNs produced by the antiviral T-cell Biofactory platform on SARS-CoV-2 infected cells and investigated the expression profiles of ISGs in the host cells in response to these IFNs. We also determined the radiation dose (γ-radiation) needed to render the T-cell Biofactory non-proliferative making the cellular products suitable for clinical use 17,[20][21][22] , while conserving the cell-based IFN production. This process ensures safe administration of the T-cell Biofactory without potential oncogenesis.…”