Recently conducted clinical trials have provided impressive evidence that chemotherapy resistant metastatic @entity320 and several @entity1583 can be cured using adoptive T cell therapy or T cell-recruiting bispecific antibodies. However, a significant fraction of @entity1 did not benefit from these treatments. Here we have evaluated the feasibility of a novel combination therapy which aims to further enhance the killing potential of bispecific antibody-redirected T lymphocytes by using these cells as targeted delivery system for photosensitizing agents. For a first in vitro proof-of-concept study, ex vivo activated @entity1 donor T cells were loaded with a @entity25210 (PSS)-complex of the model photosensitizer 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin ( @entity68421 ). In the absence of light and when loading with the water-soluble PSS/mTHPP-complex occurred at a tolerable concentration, viability and cytotoxic function of loaded T lymphocytes were not impaired. When "drug-enhanced" T cells were co-cultivated with @entity5960 -expressing @entity1 @entity189 cells, mTHPP was transferred to target cells. Notably, in the presence of a bispecific antibody, which cross-links effector and target cells thereby inducing the cytolytic activity of cytotoxic T lymphocytes, significantly more photosensitizer was transferred. Consequently, upon irradiation of co-cultures, redirected drug-loaded T cells were more effective in killing A549 lung and SKOV-3 @entity43 cells than retargeted unloaded T lymphocytes. Particularly, the additive approach using redirected unloaded T cells in combination with appropriate amounts of separately applied PSS/mTHPP was less efficient as well. Thus, by loading T lymphocytes with a stimulus-sensitive anti- @entity5 drug, we were able to enhance the cytotoxic capacity of carrier cells. @entity9335 cells could open new perspectives for adoptive T cell therapy as well as targeted photodynamic therapy.

A photosensitizer delivered by bispecific antibody redirected T lymphocytes enhances cytotoxicity against @entity5960 -expressing XXXX cells upon light irradiation.

@entity1 :: ('9606', 'Species') :: ['patients', 'human'] @entity5960 :: ('4072', 'Gene') :: ['EpCAM'] @entity43 :: ('MESH:D010051', 'Disease') :: ['ovarian carcinoma'] @entity25210 :: ('MESH:C003321', 'Chemical') :: ['poly(styrene sulfonate)'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancer'] @entity189 :: ('MESH:D002277', 'Disease') :: ['carcinoma'] @entity9335 :: ('MESH:D010787', 'Disease') :: ['Photosensitizer boosted T'] @entity1583 :: ('MESH:D019337', 'Disease') :: ['hematological malignancies'] @entity68421 :: ('MESH:C437342', 'Chemical') :: ['mTHPP'] @entity320 :: ('MESH:D008545', 'Disease') :: ['melanoma']
@entity189 :: (MESH:D002277,Disease) :: ['carcinoma']
