Advances in the treatment of metastatic clear cell renal cell carcinoma (ccRCC) have led to improved progression-free survival of many patients; however the therapies are toxic, rarely achieve durable long-term complete responses and are not curative. Herein we used a single bicistronic lentiviral vector to develop a new combination immunotherapy that consists of human anti-carbonic anhydrase IX (CAIX)-targeted chimeric antigen receptor (CAR) T cells engineered to secrete human anti-programmed death ligand 1 (PD-L1) antibodies at the tumor site. The local antibody delivery led to marked immune checkpoint blockade. Tumor growth diminished 5 times and tumor weight reduced 50–80% when compared with the anti-CAIX CAR T cells alone in a humanized mice model of ccRCC. The expression of PD-L1 and Ki67 in the tumors decreased and an increase in granzyme B levels was found in CAR T cells. The anti-PD-L1 IgG1 isotype, which is capable of mediating ADCC, was also able to recruit human NK cells to the tumor site in vivo. These armed second-generation CAR T cells empowered to secrete human anti-PD-L1 antibodies in the ccRCC milieu to combat T cell exhaustion is an innovation in this field that should provide renewed potential for CAR T cell immunotherapy of solid tumors where limited efficacy is currently seen.

No abstract

Cancers can occur in the reproductive system, such as cervix, uterus, and ovaries. These disorders affect millions of people and have no curative treatment. Recent reports revealed that the survival rates for gynecologic cancer patients are associated with immunity. In the effort of antitumor drug discovery, immunotherapies for cancer treatment have showed the potential therapeutic index and benefits to generate a greater immune response against the cancer.Reproductive Immunology: Open Access combines the viewpoints of neoplasms of the reproductive track and immunological interaction across these components.Therefore, we are delighted to invite investigators in this field for submission of any kind of articles in our journal. Editorial iMedPub Journals

No abstract