A Phase I/II Study of Intentionally Mis-Matched, Allogeneic Th1 Memory Cells (AlloStim) Conjugated With CD3/CD28-coated Microbeads in Patients With Relapsed or Refractory Hematological Malignancy
AlloStim is combination biological drug and medical device formulation consisting of
allogeneic immune cells that have been expanded and differentiated ex-vivo. These cells are
conjugated to monoclonal antibody coated microparticles prior to infusion. The immune cells
are living CD4+ memory Th1-like T-cells (T-Stim) that are differentiated from precursors
purified from normal donor blood. AlloStim is a composition of T-Stim cells conjugated to
paramagnetic epoxy covered microparticles (4.5micron) with covalently bound
anti-CD3/anti-CD28 monoclonal antibodies (Dynabeads® ClinExVivo™ CD3/CD28) at a 2:1
bead:cell ratio. The T-Stim cells are intentionally mismatched to the recipient.
The graft vs. tumor (GVT) effect that occurs after allogeneic bone marrow transplant (BMT)
is a curative therapy for advanced hematological malignancy but the clinical application of
GVT is severely limited by graft vs. host disease (GVHD) toxicity. AlloStim is designed to
elicit the "mirror" of the GVT/GVHD effects in the host immune system. Rather than trying
to separate these effects, we have proposed that the effects could remain associated and
"mirrored" onto the host immune system creating linked host vs. tumor (HVT) and host vs.
graft (HVG) effects. We hypothesized that allogeneic Th1 memory cells activated at time of
infusion to produce type 1 cytokines and express CD40L would elicit HVT/HVG "mirror effects"
in immunocompetent cancer patients.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Determination of toxicity related to AlloStim infusion in accordance with NCI Common Toxicity Criteria v.3
Within first 48 hours post infusion, at 30 days and at 60 days post infusion
Dr. Michael Har-Noy
Israel: Israeli Health Ministry Pharmaceutical Administration