A Novel Way to Fight Cancer
A Brief History of Cell-Based Immunotherapy
2 —James B. Murphy and John J. Morton (January 1915).Hence, it would seem fair to conclude that the lymphocyte is a necessary factor in cancer immunity
Clinical trial | Summary | Cancer type(s) | Sponsor/collaborators |
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NCT01807182 | ACT of TILs after combination chemotherapy | Melanoma | Fred Hutchinson Cancer Research Center; National Cancer Institute (NCI) |
NCT02652455 | ACT of TILs plus PD-1 blockade and CD137 agonism | Melanoma | H. Lee Moffitt Cancer Center and Research Institute; Bristol-Myers Squibb; Prometheus Inc.; Iovance Biotherapeutics, Inc. |
NCT00604136 | ACT of TILs | Melanoma | Hadassah Medical Organization |
NCT02354690 | ACT of TILs plus vemurafenib | Melanoma | Inge Marie Svane; Herlev Hospital |
NCT02379195 | ACT of TILs plus peginterferon | Melanoma | Inge Marie Svane; Herlev Hospital |
NCT02926053 | ACT of TILs | Renal cell carcinoma | Inge Marie Svane; Herlev Hospital |
NCT02360579 | ACT of TILs | Melanoma | Iovance Biotherapeutics, Inc. |
NCT03083873 | ACT of TILs | Squamous cell carcinoma of head and neck | Iovance Biotherapeutics, Inc. |
NCT03108495 | ACT of TILs | Cervical carcinoma | Iovance Biotherapeutics, Inc. |
NCT01946373 | ACT with or without dendritic cell vaccination | Melanoma | Karolinska University Hospital |
NCT01955460 | ACT with TGF-beta-resistant (DNRII) and NGFR-transduced T cells | Melanoma | M.D. Anderson Cancer Center; Cancer Prevention Research Institute of Texas |
NCT01740557 | ACT with T cells transduced with CXCR2 and NGFR | Melanoma | M.D. Anderson Cancer Center; National Cancer Institute (NIH/NCI); Prometheus Laboratories; Key Biologics, LLC |
NCT00338377 | ACT with or without dendritic cell immunization | Melanoma | M.D. Anderson Cancer Center; Prometheus Laboratories; Key Biologics, LLC; National Cancer Institute (NCI); Adelson Medical Research |
NCT01174121 | ACT of TILs | Gastrointestinal carcinoma, metastatic (colorectal, gastric, pancreatic, cholangio, hepatocellular) | National Cancer Institute (NCI); National Institutes of Health Clinical Center (CC) |
NCT01993719 | ACT of TILs | Melanoma | National Cancer Institute (NCI); National Institutes of Health Clinical Center (CC) |
NCT02621021 | Prospective randomized phase 2 trial of TILs plus IL-2, alone or after pembrolizumab | Melanoma | National Cancer Institute (NCI); National Institutes of Health Clinical Center (CC) |
NCT02650986 | ACT of TGFbDNRII-transduced TIL plus NY-ESO-1 reactive TCR transduced PBL | Solid tumors expressing NY-ESO-1 | Roswell Park Cancer Institute; National Cancer Institute (NCI) |
NCT03166397 | ACT of TIL | Melanoma | Sheba Medical Center |
NCT02421640 | ACT of TIL following CCR | Nasopharyngeal carcinoma | Sun Yat-sen University |
NCT02278887 | ACT of TIL versus Ipilimumab | Melanoma | The Netherlands Cancer Institute; Copenhagen University Hospital at Herlev; University of Manchester |
NCT01883297 | ACT of re-stimulated TIL plus low-dose IL-2 | Ovarian, fallopian or peritoneal cancer | University Health Network, Toronto |
NCT01883323 | ACT of TIL plus low-dose IL-2 | Melanoma | University Health Network, Toronto |
NCT02414945 | ACT of TIL plus low-dose IL-2 | Pleural mesothelioma | University Health Network, Toronto |
NCT03158935 | ACT of TIL followed by Pembrolizumab | Ovarian cancer; melanoma | University Health Network, Toronto; Merck Sharp & Dohme Corp. |
Patient Selection for Act
Relative contraindications | Age < 18 or > 70 years |
ECOG performance status > 1 | |
Unacceptable risk of sepsis or bleeding during 7–10 days of neutropenia and thrombocytopenia | |
Inability to tolerate interleukin-2 administration due to cardiopulmonary or renal insufficiency (some ACT protocols use low-dose or no IL-2) | |
Current treatment with corticosteroids or immunosuppressive agents | |
Absolute contraindications | Primary immunodeficiency or chronic viral disease (e.g., HIV, HBV, HCV) |
Pregnancy | |
Other considerations | Large, symptomatic, or bleeding CNS lesions should be treated before ACT. |
Although trial eligibility may necessitate treatment with standard-of-care therapy before ACT, metastasectomy for TIL harvest can be performed first and the T cells frozen for later use. | |
Patients in trials may require a radiographically evaluable target lesion for measurement of response to ACT. |
Operative Considerations for Til Metastasectomy
Consideration | Details |
---|---|
Tumor size | Tumor size does not correlate with TIL efficacy, but tumors should be at least 2 cm in largest diameter to obtain adequate yield of tissue for processing. |
Irradiated tumors | Avoid harvesting TILs from a tumor site that has previously been irradiated. |
Tumor site | Because TILs can be procured from a variety of tumor sites, favor surgical sites that result in minimal morbidity and consider laparoscopic approach. |
Margins | Wide surgical margins and major organ resection are not typically necessary unless the tumor resection is being performed for curative intent. Avoid cutting through tumor to minimize risk of seeding tumor site. |
Wound healing | Avoid harvest of superficial lesions if wound healing may be compromised. |
Contamination | Ulcerating tumors and those with high suspicion for bacterial colonization can result in contamination of cultures. Isolation of TILs from bowel lesions is possible but may be associated with an increased risk of contamination. |
Splenic lesions | Splenic tumors are not optimal for TILs because of theoretical concern that they may be enriched in bystander lymphocytes that are not tumor-reactive. |
CNS lesions | Tumors metastatic to CNS have not been adequately assessed as a source of TILs for treatment. |
Harvest | Refer to institutional guidelines for instructions on handling, processing, and labeling of tumor specimens. |
Confirmation | Confirmation that the metastasectomy specimen contains malignant cells will ensure that benign or nodal tissue has not been inadvertently collected. |