Human major histocompatibility complex class I chain-related A (MICA) is a human leucocyte antigen-related polymorphic molecule, which is expressed on many kinds of epithelial tumours and can be recognized by the Vd1 subset of gd T cells. In the present study, monoclonal antibodies (MoAbs) were produced in mice immunized with recombinant MICA (rMICA)*008. It was found that MICA was expressed on ovarian and colonic tumour tissues and could be detected by these anti-MICA MoAbs. The immobilized rMICA could induce the proliferation of human ovarian epithelial carcinoma-or colonic carcinomaderived gd T cells of the Vd1 phenotype in vitro. These Vd1 T cells displayed a strong, broad-range cytolytic activity towards tumour cell lines positive for MICA. The efficiency of this cytolytic activity depended greatly on the level of MICA expressed on the cell surface and could be inhibited by anti-MICA MoAbs. Therefore, MICA may play an important role in immune responses against epithelial tumours and function as a stimulating factor for the growth of Vd1 gd T cells, whereas MICA-reactive Vd1 gd T cells might serve as a new candidate for adoptive cellular therapy of tumours.
Background: The use of target therapy in lung cancer has changing the story of this disease. However, the toxicity sometimes can be a challenge. Method: We report a clinical case in a patient with advanced lung cancer with mutation in ROS 1 that had an excellent response with Crizotinib, but developed high levels of CPK. Result: Man, 75y, with an adenocarcinoma of the right lung with lesions in pleura. Tumor was assessed for EGFR mutation and ALK translocation, but were not found. We started chemotherapy with Carboplatin and Pemetrexed with partial response and, after four cycles, we continued treatment with Pemetrexed isolated. After thirteen cycles, he had bone progression and the chemotherapy was changed to Docetaxel. After that, he was submitted to three more lines of chemotherapy and immunotherapy with Nivolumabe. After four years of metastatic disease, a new bone progression with a sternal mass. new biopsy was made and found a mutation in the ROS 1 gene. He was very symptomatic, limited performance status (ecog 4) and was admmited in the hospital. We started treatment with Crizotinib 250 mg twice daily and he had a dramatic response. After two months, ECOG was one and a PET-CT showed almost a complete response. However, the patient started cramps in the abdomem and laboratory showed a CPK of 4500 u/l. the dose of the Crizotinib was adjusted to 250mg/day and the levels of cpk started to fall. We tried to reintroduce the full dose, but the levels of CPK increases to 4800 u/l again. So, we reduced the dose with maintenance of response and better tolerability. Conclusion: The increased levels of CPK with inibithors of alk is described with Alectinib. This relation with Crizotinib is not well estabilished. In this case, there was an excellent response, but the dose was limited by the increase of CPK.
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