treatment of malignant melanoma with gpa-trimar-t cell therapy

Conditions: Malignant Melanoma

Summary: malignant melanoma have been reported to be characterized with high gp100 expression. patients' autologous t cells will be isolated and transduced by gpa-trimar lentivirus to generate the gpa-trimar-t cells. when infused back to the patient, the gpa-trimar-t cells will recognize and kill target cells that express gp100(209-217) peptides in the form mhc-i complex, thus eliminating malignant melanoma from the body.

gpa-trimar is a modified chimeric antigen receptor (car) that consist of three subunit in it's outer membrane domain. the outer membrane domain linked to the inner membrane 4-1bb/cd3ζ domain through the transmembrane domain, thus compose the complete chimeric antigen receptor. patients' autologous t cells will be isolated and transduced by gpa-trimar lentivirus to generate the gpa-trimar-t cells. when infused back to the patient, the modified gpa-trimar-t cells will recognize and kill malignant melanoma cells in the body, and in the meanwhile the other two subunits function to stimulate the innate immune system and enhance gpa-trimar-t cells tumor infiltration.

Eligibility criteria:
inclusion criteria: 1. all subjects must personally sign and date the consent form before initiating any study specific procedures or activities; 2. all subjects must be able to comply with all the scheduled procedures in the study; 3. hla_a2 genotype and gp100 positive malignant melanoma： ⅳ stage or relapsed after surgery or chemotherapy or no available standard therapy; 4. at least one measurable lesion per recist v1.1; 5. aged 18 to 69 years; 6. expected survival ≥12 weeks; eastern cooperative oncology group (ecog) performance status of≤2; 7. systematic usage of immunosuppressive drug or corticosteroid must have been stopped for more than 4 weeks; 8. all other treatment induced adverse events must have been resolved to ≤grade 1; 9. laboratory tests must fulfill the following criteria: anc ≥ 1000/ul, hgb\>70g/l, platelet count ≥ 50,000/ul, creatinine clearance ≤1.5 uln, serum alt/ast ≤2.5 uln, total bilirubin ≤1.5 uln (except in subjects with gilbert's syndrome); exclusion criteria: 1. presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring iv antimicrobials for management. (simple uti and uncomplicated bacterial pharyngitis are permitted if responding to active treatment); 2. patients with symptomatic central nervous system metastasis, intracranial metastasis, and cancer cells found in cerebrospinal fluid are not recommended to participate in this study. symptom free or post-treatment stable disease or disappearance of lesions should not be excluded. the specific selection is ultimately determined by the investigator; 3. lactating women or women of childbearing age who plan to conceive during the time period; 4. active infection with hepatitis b (hbsag positive) or hepatitis c virus (anti-hcv positive); 5. known history of infection with hiv; 6. subjects need systematic usage of corticosteroid; 7. subjects need systematic usage of immunosuppressive drug; 8. planed operation, history of other related disease, or any other related laboratory tests restrict patients for the study; 9. other reasons the investigator consider the patient may not be suitable for the study.

Keywords: hla-a2 gp100