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Personalized TIL cellular therapy. Significant in-patient hospital stay (Bethesda, MD). Requires a tumor deemed by the trial MD to be large enough & surgically harvestable.

Clinical paper of MSS-CRC Success: https://www.ncbi.nlm.nih.gov/pubmed/27959684

We identified a polyclonal CD8+ T-cell response against mutant KRAS G12D in tumor-infiltrating lymphocytes obtained from a patient with metastatic colorectal cancer. We observed objective regression of all seven lung metastases after the infusion of approximately 1.11×1011 HLA-C*08:02–restricted tumor-infiltrating lymphocytes that were composed of four different T-cell clonotypes that specifically targeted KRAS G12D. However, one of these lesions had progressed on evaluation 9 months after therapy. The lesion was resected and found to have lost the chromosome 6 haplotype encoding the HLA-C*08:02 class I major histocompatibility complex (MHC) molecule. The loss of expression of this molecule provided a direct mechanism of tumor immune evasion. Thus, the infusion of CD8+ cells targeting mutant KRAS mediated effective antitumor immunotherapy against a cancer that expressed mutant KRAS G12D and HLA-C*08:02.

Above Patient’s perspective: http://cancerriot.blogspot.com/p/procedures.html

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纳入标准

* 纳入标准：
* Measurable (per RECIST v1.0 criteria), metastatic cancer of one of the following types: upper or lower gastrointestinal, hepatobiliary, genitourinary, breast, ovarian/endometrial, or endocrine tumors including neuroendocrine tumors. Patients must have at least one lesion that is resectable for TIL generation with minimal morbidity, preferentially using minimal invasive laparoscopic or thoracoscopic surgery for removal of superficial tumor deposit.
* Confirmation of diagnosis of metastatic cancer by the NCI Laboratory of Pathology.
* 对已获批准的标准系统疗法难治。特别是

* Patients with metastatic colorectal cancer must have received oxaliplatin or irinotecan.
* Patients with hepatocellular carcinoma must have received sorafenib (Nexavar(R)), since level 1 data support a survival benefit with this agent.
* Patients with breast and ovarian cancer must be refractory to both first- and second-line treatments and must have received at least one second-line chemotherapy regimen.
* Patients with 3 or fewer brain metastases that are < 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for one month after treatment for the patient to be eligible. Patients with surgically resected brain metastases are eligible. * Age greater than or equal to 18 years and less than or equal to 72 years. * Clinical performance status of ECOG 0 or 1. * Patients of both sexes must be willing to practice birth control from the time of enrollment on this study and 12 months after the last dose of combined chemotherapy for individuals of child-bearing potential (IOCBP) and for four months after treatment for individuals that can father children. * IOCBP must have a negative pregnancy test be a pregnancy test prior to the start of treatment because of the potentially dangerous effects of the treatment on the fetus. Serology * Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive may have decreased immune-competence and thus may be less responsive to the experimental treatment and more susceptible to its toxicities.) * Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then the patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative. Hematology * ANC > 1000/mm^3 而不使用非格司亭
* 白细胞大于或等于 2500/mm^3
* 血小板计数大于或等于 80,000/mm^3
* 血红蛋白 > 8.0 g/dL。受试者可通过输血达到这一临界值。

化学

* 血清 ALT/AST 小于或等于 5.0 x ULN
* Serum creatinine less than or equal to 1.5 x ULN
* 总胆红素小于或等于 2.0 毫克/分升，吉尔伯特综合征患者除外，他们的总胆红素必须小于 3.0 毫克/分升。
* 患者在入组时必须已完成之前的任何系统治疗。

注：只要相关的主要器官毒性已恢复到小于或等于 1 级，患者可在入组前四周内接受过小型外科手术或有限的野外放疗。

* 受试者能够理解并愿意签署书面知情同意书。
* 愿意签署持久授权书。
* 受试者必须同时加入 03-C-0277 方案。

排除标准

排除标准：

* Participants who are pregnant or nursing because of the potentially dangerous effects of the treatment on the fetus or infant.
* 同时接受全身类固醇治疗。
* 需要抗感染治疗的活动性全身感染、凝血功能障碍或任何其他活动性或无补偿的重大疾病。
* Advanced primary with impeding occlusion, perforation or bleeding, dependent on transfusion.
* 任何形式的原发性免疫缺陷（如严重联合免疫缺陷病和艾滋病）。
* 有主要器官自身免疫疾病史。
* Grade 3 or 4 major organ irAEs clinically attributed to anti-PD-1/PD-L1 therapy.
* Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immunecompetence may be less responsive to the experimental treatment and more susceptible to its toxicities.)
* 对环磷酰胺、氟达拉滨或阿糖胞苷有严重的即刻超敏反应史。
* 有冠状动脉血管重建史或缺血性症状。
* 对于有临床病史、需要进行心脏评估的特定患者：最后已知的 LVEF 小于或等于 45%。
* Documented Child-Pugh score of B or C for hepatocellular carcinoma patients with known underlying liver dysfunction.
* For select patients with a clinical history prompting pulmonary evaluation: known FEV1 less than or equal to 50%.
* 正在接受其他研究药物治疗的患者。