Anticancer therapy Tumor-infiltrating<unk> s have been reported to play a critical role in promoting drug-induced cell death in human triple-negative breast cancer. Since<unk> s recognize target cells when they express nonself HLA antigens (but not self), autologous (patients' own)<unk>  infusions have not shown any antitumor effects. Instead, investigators are working on using allogeneic cells from peripheral blood, which requires that all T cells be removed before infusion into the patients to remove the risk of graft versus host disease, which can be fatal. This can be achieved using an immunomagnetic column (CliniMACS). In addition, because of the limited number of<unk> s in blood (only 10% of lymphocytes are<unk> s), their number needs to be expanded in culture. This can take a few weeks and the yield is donor-dependent.<unk> -92 cells A more efficient way to obtain high numbers of<unk> s is to expand<unk> -92 cells, an<unk>  line with all the characteristics of highly active blood Natural<unk>  <unk> s but with much broader and higher cytotoxicity.<unk> -92 cells grow continuously in culture and can be expanded to clinical-grade numbers in bags or bioreactors. Clinical studies have shown<unk> -92 cells to be safe and to exhibit anti-tumor activity in patients with lung or pancreatic cancer, melanoma, and lymphoma. Because<unk> -92 cells originated from a patient with lymphoma, they must be irradiated prior to infusion. although efforts are being made to engineer the cells to eliminate the need for irradiation. The irradiated cells maintain full cytotoxicity.<unk> -92 are allogeneic (from a donor different from the recipient), but in clinical studies have not been shown to elicit significant host reaction. Unmodified<unk> -92 cells lack CD-16, making them unable to perform antibody-dependent cellular cytotoxicity (ADCC); however, the cells have been engineered to express a high affinity Fc-receptor (CD16A, 158V) genetically linked to IL-2 that is bound to the endoplasmic reticulum (ER). These high affinity<unk> -92 cells can perform ADCC and have greatly expanded therapeutic utility.<unk> -92 cells have also been engineered to expressed chimeric antigen receptors (CARs), in an approach similar to that used for T cells. An example of this is an<unk> -92 derived cell engineered with both a CD16 and an anti-PD-L1 CAR; currently in clinical development for oncology indications A clinical grade<unk> -92 variant that expresses a CAR for HER2 (ErbB2) has been generated and is in a clinical study in patients with HER2 positive glioblastoma. Several other clinical grade clones have been generated expressing the CARs for PD-L1, CD19, HER-2, and EGFR. PD-L1 targeted high affinity<unk> s have been given to a number of patients with solid tumors in a phase I/II study, which is underway.<unk> G2D-Fc Fusion Protein In a study at Boston Children's Hospital, in coordination with Dana-Farber Cancer Institute, in which immunocompromised mice had contracted lymphomas from EBV infection, an<unk> -activating receptor called<unk> G2D was fused with a stimulatory Fc portion of the EBV antibody. The<unk> G2D-Fc fusion proved capable of reducing tumor growth and prolonging survival of the recipients. In a transplantation model of LMP1-fueled lymphomas, the<unk> G2D-Fc fusion proved capable of reducing tumor growth and prolonging survival of the recipients. In Hodgkin lymphoma, in which the malignant Hodgkin Reed-Sternberg cells are typically HLA class I deficient, immune evasion is in part mediated by skewing towards an exhausted PD-1hi<unk>  phenotype, and re-activation of these<unk> s appears to be one mechanism of action induced by checkpoint-blockade.
Natural killer cell
Natural killer T cell
T cell
Cytokine-induced killer cell
Dendritic cell
Reactive lymphocyte
Mast cell
Monocyte