Donor Derived NK Cell Product for Adoptive Cell-Mediated Immune therapy
Gamida Cell has developed a novel propriety technology for the expansion of natural killer (NK) cells. The technology is now being translated into a cell product for immunotherapy of metastatic solid tumors and refractory hematological malignancies.
Clinical Applicability of NK Cells in Adoptive Cell-Mediated Immune Therapy
Natural Killer (NK) cells are cytotoxic lymphocytes that have drawn considerable attention in recent years as a promising tool for cell therapy of cancer. NK cells were originally identified and distinguished from T cytotoxic lymphocytes by their capacity for "natural" cytotoxicity, the ability to kill tumor target cells in the absence of prior sensitization. Adoptive NK cell immunotherapy strategies appear to be promising owing to their enhanced anti-tumor effects without increasing the risk of GvHD.
Clinical trials are evaluating the safety and efficacy of donor NK cell infusion in cancer patients with Multiple Myeloma, Neuroblastoma, Hepatocellular carcinoma, Sarcoma family of tumors (Cancer Immunol Immunother. 2010 Aug 12) and hematological malignancies (Immunol Rev. 2008 Aug;224:58-69). Promising outcomes of safety and efficacy have been demonstrated.
In most of these studies, NK cells were obtained from a family member of the patient who is a partial match (haplo identical) to the patient's immune type (HLA type).The main obstacle in clinical studies with NK cells originates from the fact that the cells need to be activated before infusion and that they are present in insufficient numbers in peripheral blood mononuclear cells. Once activated, NK cells produce immune regulatory cytokines, interact with other immune cells and finally destroy tumour and pathogen-infected cells. However, during activation in culture, NK cells lose some of their capability to traffic, to localize and to proliferate. This has been suggested as a major cause for the poor in-vivo survival of adoptively transferred immune cells, a limitation that may have a direct and a considerable impact on their clinical efficacy.
Gamida Cell proprietary technology and pre-clinical data
NK cells hardly proliferate in cultures stimulated with only growth factors. The protocols commonly used for NK expansion include feeder cells and/or cGMP-incompatible components. These disadvantages render such protocols either expensive or suboptimal for GMP production and unfeasible for large-scale clinical studies.
Using a small molecule as the active ingredient, Gamida Cell developed a novel, simple and robust epigenetic technology for prompt expansion and activation of NK cells in feeder free conditions. Starting the ex vivo cultures with donor derived peripheral blood cells depleted of T cells, following 14 days incubation, the expanded cell population comprises a highly purified NK cell fraction with less than one percent contamination of T cells.
NK cells expanded in culture using this novel technology display increased tumor killing ability. They migrate with higher efficacy and express significantly higher levels of cell receptors shown to be pivotal for NK cells trafficking to the lymphoid organs and for the prolonged homeostatic proliferation (J.Immunol. 2009;183;3219-3228).
Our animal studies clearly demonstrate that following infusion, the cells localize to the target tissues with higher efficacy and most importantly, their in vivo survival is substantially enhanced, essential for the successful adoptive immunotherapy approaches of cancer (Fig 1).
These intriguing findings encouraged Gamida Cell to move forward to develop a cell product for adoptive cell-mediated immune therapy, to treat metastatic solid tumors and refractory hematological malignancies.
Fig.1: Engraftment of NK cells