Table 3.
Biotech companies/Universities entering into personalized medicine targeting intracellular immune checkpoints in combination with ICB-therapeutics.
| Biopharmaceutical Company/University | Target | Combined Therapeutic Approach |
Clinical Trial | Indication | Ref. |
|---|---|---|---|---|---|
| Natural Killer Cells (NK-cells) Clinicaltrials.gov, accessed on 15 July 2021 | |||||
| ONK therapeutics (Ireland) 2015 www.onktherapeutics.com | CISH−/− NK-cells NK-cells |
CISH−/− NK-cells in combination with ICB-antibodies |
ONK102 ONK103 ONK104 |
M. Myeloma NSCLC AML |
[135] |
| Fate Therapeutics San Diego, USA |
iPSC-derived NK Cells (FT500) | Nivolumab (anti-PD-1) Pembrolizumab (anti-PD-1) Atezolizumab (anti-PD-L1) Interleukin-2 (IL-2) |
NCT03841110 NCT04106167 (Phase-I) |
Advanced solid tumors and lymphoma |
[136,137,138,139,140] |
| Innate Pharma S. A |
NK cell (NKG2A) | Durvalumab (Phase-I/II) Nivolumab (Phase-I) Ipilimumab (Phase-I) Nivolumab + 5-Aza (Ph-I) |
NCT02671435 NCT01592370 NCT01750580 NCT02599649 |
Metastatic Cancer | [141,142] |
| Altor Biosciences corporation |
IL-15 super agonist mediated NK-cells | Nivolumab (anti-PD-1) |
NCT02523469 (Phase-I/II) |
NSCLC | [142] |
| ImmunityBio, Inc. | High-affinity Natural Killer (haNK) Cell | Avelumab (Bavencio®) (anti-PD-L1) |
NCT03387085 (Phase-I/II) |
Triple Negative Breast Cancer | - |
| SignalRX Pharmaceuticals, Inc. | SF1126 (dual inhibitor of PI3K and BRD4) |
Nivolumab (anti-PD-1) | NCT03059147 | Advanced HCC | [83] |
| Effector Therapeutics | Tomivosertib (eFT-508) | Pembrolizumab (anti-PD-1) |
NCT03616834 Phase-II Completed 2021 |
Solid tumors and NSCLC | [83] |
| NantKwest Inc., and Chan Soon-Shiong Institute for Medicine, USA | CD16-targeted NK-cell (haNKTM) with N-803 (IL-15 superagonist) | Avelumab (Bavencio®) (anti-PD-L1) |
NCT03853317 (Phase-II) |
Merkel cell carcinoma | [139,143] |
| National Cancer Institute, Naples | NK-cells (Tregs and NKs) |
Nivolumab (anti-PD-1) | NCT03891485 | Renal cell carcinoma | [144] |
| Gachon University & Severance hospital, Republic of Korea | Allogeneic NK-Cells (SMT-NK) | Pembrolizumab (anti-PD-1) Keytruda |
NCT03937895 (Phase-I/II) |
Biliary tract cancer | [139] |
| Fox Chase Cancer Center, USA | NK-cells and T-cells | Pembrolizumab (anti-PD-1) |
NCT02535247 (Phase-I/II) |
Lymphoma | [144,145,146] |
| Jilin University Hospital, China | NK-cells | PD-1 Ab |
NCT03958097 (Phase-II) |
Non-small cell lung cancer | [139] |
| MD Anderson Cancer Center, USA | DF1001 (a new molecule targeting NK-cell activations) |
Drug: DF1001 Pembrolizumab (anti-PD-1) |
NCT04143711 (Phase-I/II) |
Advanced Solid Tumors | [139,144] |
| T-Cells: Tumor-Infiltrating Lymphocytes (TILs) | |||||
| Intima Bioscience, Inc. with University of Minnesota |
CISH-deleted Tumor-Infiltrating Lymphocytes (TIL) | CISH checkpoint-deleted TILs combined with Cyclophosphamide, Fludarabine, Aldesleukin and ICB-therapeutics |
NCT04426669 (Phase-I/II) |
Solid tumors & gastro-intestinal cancers | [1,147] |
| CISH−/− T-cells (TILs) | NCT03538613 (Phase-I/II) |
Gastro-intestinal cancers | [2,5] | ||
| Hangzhou Cancer Hospital in collabration with Anhui Kedgene Biotechnology Co.,Ltd | PD-1 Knockout T-Cells | CRISPR/Cas9-deleted PD-1 in T-Cells with hydrocortisone |
NCT03081715 (Phase-I) Completed, 2018 |
Advanced Esophageal Squamous Cell Carcinoma | [2,144] |
| Sichuan University in collabration with Chengdu MedGenCell |
PD-1 Knockout T-Cells | CRISPR/Cas9-deleted PD-1 in T-Cells with Cyclophosphamide |
NCT02793856 (Phase-I) Completed, 2020 |
Metastatic Non-small Cell Lung Cancer | [2,144,148] |
| Peking University and (Cell Biotech) |
PD-1 Knockout Engineered T Cells | PD-1-KO-T-cells with IL-2 and Cyclophosphamide |
NCT02863913 NCT02867345 NCT02867332 (Phase-I) |
Bladder, Prostate and Renal Cell Carcinoma | [2,5] |
| University of Pennsylvania, with Tmunity Therapeutics |
NY-ESO-1 redirected autologous T cells | TCR-deleted and PD-1-deleted T cells |
NCT03399448 | Myeloma, melanoma and several cancers | [2,5,149] |
| Nanjing University Medical School | PD-1 Knockout EBV-CTLs | PD-1-KO-EBV-CTL with IL-2, Fludarabine and Cyclophosphamide |
NCT03044743 (Phase-I/II) |
EBV associated Malignancies | [2,5] |
| Dendritic Cells (DCs) | |||||
| H. Lee Moffitt Cancer Center, BMS and MultiVir, Inc. | DC-based p53 Vaccine | Ipilimumab (anti-CTLA4) Nivolumab (anti-PD-1) |
NCT03406715 (Phase-II) |
Small Cell Lung Cancer | [137] |
| Allife Medical Sc. and Technology Co., Ltd. | DC-NK YNYY-01 (DC-NK Cells) |
Pembrolizumab (anti-PD-1) Keytruda |
NCT03815084 (Phase-I) |
Solid tumors | [144,150] |
| Bristol-Myers Squibb and Duke Cancer Inst. |
DC Vaccines | Nivolumab (anti-PD-1) |
NCT02529072 NCT02775292 (Phase-I) |
Recurrent Brain Tumors | |
| Northwest Biotherapeutics, BMS and JCCC | Autologous DCs pulsed with tumor lysate | Nivolumab (anti-PD-1) |
NCT03014804 (Phase-II) |
Recurrent Glioblastoma | |
| University of Pennsylvania | Autologous DC pulsed peptide | Pembrolizumab (anti-PD-1) |
NCT03092453 (Phase-I) |
Advanced Melanoma | |
| Mayo Clinic in collabration with National Cancer Inst. | Autologous DC pulsed tumor Ags | Pembrolizumab (anti-PD-1) |
NCT03035331 (Phase-I/II) |
Aggressive Non-Hodgkin Lymphoma | |
| Oslo University Hospital in collabration with NCS and MSDC | Autologous DC | Pembrolizumab (anti-PD-1) Rituximab, GM-CSF and anti-TNF-alpha therapy |
NCT02677155 (Phase-II) |
Follicular Lymphoma | |
| Capital Medical Univ. in collabration with Duke Univ. | Autologous DC-CIK cell | Pembrolizumab Anti-PD-1 + DC-CIK (Ph-I) Anti-PD-1 alone (Ph-II) |
NCT03190811 NCT03360630 |
Advanced Solid Tumors and NSCLC |
|
| Sun Yat-sen University | DC-CIK cell (Cytokine-induced Killer Cell) |
Anti-PD-1 antibody |
NCT02886897 (Phase-I) Completed, 2019 |
Refractory Solid Tumors | |
| Beth Israel Deaconess Medical Center | Dendritic Cell Fusion Vaccine | Pidilizumab (anti-PD-1) |
NCT01067287 (Phase-I) |
Multiple Myeloma | |
| Cancer Insight in collabration with Elios Therapeutics, LLC | Autologous DC (TLPLDC Vaccine) | Checkpoint Inhibitor |
NCT02678741 (Phase-I/II) |
Metastatic Melanoma | |
| Grupo Espanol Multidisciplinario del Cancer Digestivo | Autologous DC Vaccine (AVEVAC) | Avelumab (Bavencio®) (anti-PD-L1) |
NCT03152565 (Phase-I/II) Completed, 2020 |
Metastatic Colorectal Carcinoma | |
| Dana-Farber Cancer Institute in collabration with Celgene | DC/AML Fusion Vaccine | Durvalumab (Imfinzi®) (anti-PD-L1) |
NCT03059485 (Phase-II) |
Acute Myelogenous Leukemia | |
| Radboud University in collabration with Dutch Cancer Society |
MiHA-loaded PD-L1/L2 silenced DC Vaccination | PD-L1/L2-silenced DC (siRNA silenced) |
NCT02528682 (Phase-I/II) Completed, 2021 |
Hematological Malignancies | |
| Johns Hopkins University, USA | TLR3 agonist enhace DC activation | Anti-PD-1 in combination with DCs | - | Glioblastoma | [16] |