Immune checkpoint inhibitor (ICI) and CAR-T cell immunotherapies have provided new treatment options for many patients with metastatic disease and hematological malignancy, respectively, inducing durable responses in some cases. CAR-T is not indicated for solid tumors and ICI responsiveness requires high tumor mutational load, CD8+ T cell infiltration and positive IFN-γ status, defining an inflamed phenotype (“hot tumors”). However, the majority of metastatic tumors present as non-inflamed (“cold tumors”), thus limiting the applicability of ICI to a minority subset of patients with highly immunogenic tumors. Immunological treatment of cold tumors is a great challenge as no pre-existing adaptive immune response has been established or maintained.
AlloStim®, was used on compassionate grounds AlloStim® is currently being evaluated in a phase IIB clinical trial in USA in MSI-S, chemotherapy-refractory, metastatic colorectal cancer patients, an indication known to present with “cold” lesions and to be non-responsive to ICI. AlloStim® is a living, non-genetically manipulated, allogeneic Th1-like cell therapy derived from precursor cells purified, expanded and differentiated from blood of normal donors. The AlloStim® mechanism of action is purported to convert “cold” tumors to “hot” tumors and naturally down-regulate checkpoint molecules in the tumor microenvironment. Single dose vials of formulated AlloStim® cells were delivered to our center in liquid nitrogen dry shippers. Administered either intradermally (ID) or intravenously (IV). The protocol included 3 weekly intradermal (ID) injections followed a week later by an intravenous (IV) infusion. This 4-week cycle was repeated 3 times. Upon approval of our institutional review board and obtaining informed consent.
7 patients were acured 3 advanced/metastatic hepatocellular carcinoma, 2 breast cancer, 1 gall bladder and 1 Nasopharyngeal cancer. Due to the advanced status and poor ECOG status, only 3 completed the treatment schedule. 2 were still stable and alive at 1-year follow-up without receiving any other systemic therapy.
Simple to administer, minimal side-effects and appears to have activity in refractory metastatic disease. Further controlled clinical trials is warranted.
Has not received any funding.
M. Har Noy: Leadership role, Shareholder/Stockholder/Stock options, Officer/Board of Directors: Mirror Biologics Inc. All other authors have declared no conflicts of interest.