We chose a complementary approach, focusing on innate immunity. Clinical trials have tested numerous strategies for re-activating lymphocytes and other leukocyte subsets. Based on these observations it was posed that the anti-inflammatory environment of the tumor inhibited a de novo immune response. Shortly thereafter, the FDA approved Axicabtagene ciloleucel for the treatment of diffuse large B cell lymphoma.ĪCT is derived from the observations that immune cells recognize and kill cancer cells. The CAR approach has been reproducibly successful in targeting CD19 in B cell acute lymphoblastic leukemia (ALL), leading to the first Federal Drug Administration (FDA) approval of Tisagenlecleucel in 2017. Since then, autologous cellular immunotherapy approaches have expanded from using endogenous TILs to engineering cells to express selected T cell receptors or to express chimeric antigen receptors that are not restricted by HLA type. All of the elutriated cell fractions contain ample immune cells which could be used for other cell therapy-based applications.Īdoptive cell therapy (ACT) for the treatment of cancer was pioneered in the 1980s using T cells harvested from the patients’ own tumors. These monocytes can be cryopreserved and maintain viability and cytotoxic function. Large scale isolation of monocytes from both healthy donors and patients with advanced, chemotherapy resistant ovarian cancer, can be achieved with high total number of monocytes. We also show that the monocytes are stable, viable, and retain cytotoxic functions when cultured with IFNs. Resultsīoth iterative monocyte isolation using counter flow elutriation or cryopreservation following counter flow elutriation can yield over 2 billion monocytes for each donor with high purity. All five fractions obtained from the elutriation procedure were also assessed by flow cytometry to measure the percent of immune cell subsets in each fraction. The monocyte-containing, RO-fraction was assessed for total monocyte number, purity, viability, and cytotoxicity with and without a cryopreservation step. MethodsĬounter flow elutriation was performed on healthy donors or women with ovarian cancer. Here we describe the optimization of the monocyte elutriation protocol and a cryopreservation protocol of the monocytes isolated from peripheral blood. We translated these observations to an ongoing clinical trial using adoptive cell transfer of autologous monocytes stimulated ex vivo with IFNs and infused into the peritoneal cavity of patients with advanced, chemotherapy resistant, ovarian cancer. We have previously shown that monocytes stimulated with both interferons (IFNs) results in synergistic killing of ovarian cancer cells. Monocytes have been shown to be cytotoxic to tumor cells in the presence of pro-inflammatory cytokines such as Interferon Alpha, Interferon Gamma, and IL-6. At the site of inflammation, monocytes express cytokines and chemokines. Monocytes are myeloid cells that reside in the blood and bone marrow and respond to inflammation.
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