Emerging Trends in Immunotherapy for Cancer
Abstract
:1. Introduction
2. Cancer Immunity and Immune Evasion
3. Immune Checkpoints
3.1. Adaptive Immune Checkpoints
3.1.1. CTLA-4
3.1.2. PD-1
3.1.3. LAG-3
3.1.4. TIGIT
3.1.5. TIM-3
3.1.6. B7-H3 and B7-H4
3.1.7. VISTA
3.1.8. OX40/OX40L
3.1.9. A2A/B-R and CD73
3.1.10. NKG2A
3.2. Innate Immune Checkpoints
3.2.1. SIRPα-CD47
3.2.2. LILRB1/MHC-I and LILRB2/MHC-I
3.2.3. Siglec10-CD24
3.2.4. APMAP
3.3. Trends in Clinical Trials with Immune Checkpoint Inhibitors
3.4. Limitations and Challenges of ICI Therapy
4. Adoptive Cell Therapy
4.1. TILs (Tumor-Infiltrating Lymphocytes)
4.2. TCR (T Cell Receptor) Therapy
4.3. CAR T Cells
4.4. CAR-NK Cells
4.5. Limitations and Challenges of CAR T Therapy
5. Monoclonal Antibodies
5.1. Direct Killing and Immune-Mediated Killing
5.2. mAbs Targeting Angiogenesis
5.3. Antibody-Drug Conjugates
5.4. Antibody Radioimmunoconjugate (RIC)
5.5. Bispecific Antibodies
6. Cytokine Therapies
Limitations and Challenges of Cytokine Therapy
7. Oncolytic Viruses
Limitations and Challenges of OV Therapy
8. Cancer Vaccines
Limitations and Challenges of Cancer Vaccines
9. Conclusions and Future Perspectives
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- McCarthy, E.F. The toxins of William B. Coley and the treatment of bone and soft-tissue sarcomas. Iowa Orthop. J. 2006, 26, 154–158. [Google Scholar] [PubMed]
- Hayre, D.S. 23. Coley’s toxin and spontaneous tumour regression. Clin. Investig. Med. 2007, 30, 39–40. [Google Scholar] [CrossRef]
- Kramer, M.G.; Masner, M.; Ferreira, F.A.; Hoffman, R.M. Bacterial Therapy of Cancer: Promises, Limitations, and Insights for Future Directions. Front. Microbiol. 2018, 9, 16. [Google Scholar] [CrossRef] [PubMed]
- Oiseth, S.J.; Aziz, M.S. Cancer immunotherapy: A brief review of the history, possibilities, and challenges ahead. J. Cancer Metastasis Treat. 2017, 3, 250. [Google Scholar] [CrossRef]
- Bhatia, A.; Kumar, Y. Cellular and molecular mechanisms in cancer immune escape: A comprehensive review. Expert Rev. Clin. Immunol. 2014, 10, 41–62. [Google Scholar] [CrossRef]
- Dunn, G.P.; Bruce, A.T.; Ikeda, H.; Old, L.J.; Schreiber, R.D. Cancer immunoediting: From immunosurveillance to tumor escape. Nat. Immunol. 2002, 3, 991–998. [Google Scholar] [CrossRef]
- Smyth, M.J.; Dunn, G.P.; Schreiber, R.D. Cancer Immunosurveillance and Immunoediting: The Roles of Immunity in Suppressing Tumor Development and Sha** Tumor Immunogenicity. Adv. Immunol. 2006, 90, 1–50. [Google Scholar]
- Dunn, G.P.; Old, L.J.; Schreiber, R.D. The three Es of cancer immunoediting. Annu. Rev. Immunol. 2004, 22, 329–360. [Google Scholar] [CrossRef]
- Koebel, C.M.; Vermi, W.; Swann, J.B.; Zerafa, N.; Rodig, S.J.; Old, L.J.; Smyth, M.J.; Schreiber, R.D. Adaptive immunity maintains occult cancer in an equilibrium state. Nature 2007, 450, 903–907. [Google Scholar] [CrossRef]
- Zitvogel, L.; Tesniere, A.; Kroemer, G. Cancer despite immunosurveillance: Immunoselection and immunosubversion. Nat. Rev. Immunol. 2006, 6, 715–727. [Google Scholar] [CrossRef]
- Vesely, M.; Schreiber, R.D. Cancer immunoediting: Antigens, mechanisms, and implications to cancer immunotherapy. Ann. N. Y. Acad. Sci. 2013, 1284, 1–5. [Google Scholar] [CrossRef] [Green Version]
- Yang, Y. Cancer immunotherapy: Harnessing the immune system to battle cancer. J. Clin. Investig. 2015, 125, 3335–3337. [Google Scholar] [CrossRef]
- Lentz, R.W.; Colton, M.D.; Mitra, S.S.; Messersmith, W.A. Innate Immune Checkpoint Inhibitors: The Next Breakthrough in Medical Oncology? Mol. Cancer Ther. 2021, 20, 961–974. [Google Scholar] [CrossRef]
- Ghahremanloo, A.; Soltani, A.; Modaresi, S.M.S.; Hashemy, S.I. Recent advances in the clinical development of immune checkpoint blockade therapy. Cell. Oncol. 2019, 42, 609–626. [Google Scholar] [CrossRef]
- Hargadon, K.M.; Johnson, C.E.; Williams, C.J. Immune checkpoint blockade therapy for cancer: An overview of FDA-approved immune checkpoint inhibitors. Int. Immunopharmacol. 2018, 62, 29–39. [Google Scholar] [CrossRef]
- Nirschl, C.J.; Drake, C.G. Molecular Pathways: Coexpression of Immune Checkpoint Molecules: Signaling Pathways and Implications for Cancer Immunotherapy. Clin. Cancer Res. 2013, 19, 4917–4924. [Google Scholar] [CrossRef]
- Dunn, G.P.; Old, L.J.; Schreiber, R.D. The immunobiology of cancer immunosurveillance and immunoediting. Immunity 2004, 21, 137–148. [Google Scholar] [CrossRef]
- Chen, D.S.; Mellman, I. Elements of cancer immunity and the cancer-immune set point. Nature 2007, 541, 321–330. [Google Scholar] [CrossRef]
- Liu, J.-N.; Kong, X.-S.; Huang, T.; Wang, R.; Li, W.; Chen, Q.-F. Clinical Implications of Aberrant PD-1 and CTLA4 Expression for Cancer Immunity and Prognosis: A Pan-Cancer Study. Front. Immunol. 2020, 11, 2048. [Google Scholar] [CrossRef]
- Dovedi, S.J.; Elder, M.J.; Yang, C.; Sitnikova, S.I.; Irving, L.; Hansen, A.; Hair, J.; Jones, D.C.; Hasani, S.; Wang, B.; et al. Design and Efficacy of a Monovalent Bispecific PD-1/CTLA4 Antibody That Enhances CTLA4 Blockade on PD-1+ Activated T Cells. Cancer Discov. 2021, 11, 1100–1117. [Google Scholar] [CrossRef]
- Buchbinder, E.I.; Desai, A. CTLA-4 and PD-1 pathways similarities, differences, and implications of their inhibition. Am. J. Clin. Oncol. Cancer Clin. Trials 2016, 39, 98–106. [Google Scholar]
- Takahashi, T.; Tagami, T.; Yamazaki, S.; Uede, T.; Shimizu, J.; Sakaguchi, N.; Mak, T.W.; Sakaguchi, S. Immunologic Self-Tolerance Maintained by Cd25+Cd4+Regulatory T Cells Constitutively Expressing Cytotoxic T Lymphocyte–Associated Antigen 4. J. Exp. Med. 2000, 192, 303–310. [Google Scholar] [CrossRef] [PubMed]
- Schadendorf, D.; Hodi, F.S.; Robert, C.; Weber, J.S.; Margolin, K.; Hamid, O.; Patt, D.; Chen, T.-T.; Berman, D.M.; Wolchok, J.D. Pooled Analysis of Long-Term Survival Data From Phase II and Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma. J. Clin. Oncol. 2015, 33, 1889–1894. [Google Scholar] [CrossRef] [PubMed]
- Postow, M.A.; Chesney, J.; Pavlick, A.C.; Robert, C.; Grossmann, K.; McDermott, D.; Linette, G.P.; Meyer, N.; Giguere, J.K.; Agarwala, S.S.; et al. Nivolumab and Ipilimumab versus Ipilimumab in Untreated Melanoma. N. Engl. J. Med. 2015, 372, 2006–2017. [Google Scholar] [CrossRef]
- Larkin, J.; Chiarion-Sileni, V.; Gonzalez, R.; Grob, J.-J.; Cowey, C.L.; Lao, C.D.; Schadendorf, D.; Dummer, R.; Smylie, M.; Rutkowski, P.; et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N. Engl. J. Med. 2015, 373, 23–34. [Google Scholar] [CrossRef]
- Wolchok, J.D.; Chiarion-Sileni, V.; Gonzalez, R.; Grob, J.-J.; Rutkowski, P.; Lao, C.D.; Cowey, C.L.; Schadendorf, D.; Wagstaff, J.; Dummer, R.; et al. Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone Versus Ipilimumab in Patients With Advanced Melanoma. J. Clin. Oncol. 2022, 40, 127–137. [Google Scholar] [CrossRef]
- Kamatham, S.; Shahjehan, F.; Kasi, P.M. Immune Checkpoint Inhibitors in Metastatic Colorectal Cancer: Current Status, Recent Advances, and Future Directions. Curr. Colorectal Cancer Rep. 2019, 15, 112–121. [Google Scholar] [CrossRef]
- Morse, M.A.; Hochster, H.; Benson, A. Perspectives on Treatment of Metastatic Colorectal Cancer with Immune Checkpoint Inhibitor Therapy. Oncologist 2019, 25, 33–45. [Google Scholar] [CrossRef]
- Saung, M.T.; Pelosof, L.; Casak, S.; Donoghue, M.; Lemery, S.; Yuan, M.; Rodriguez, L.; Schotland, P.; Chuk, M.; Davis, G.; et al. FDA Approval Summary: Nivolumab Plus Ipilimumab for the Treatment of Patients with Hepatocellular Carcinoma Previously Treated with Sorafenib. Oncologist 2021, 26, 797–806. [Google Scholar] [CrossRef]
- Baas, P.; Scherpereel, A.; Nowak, A.K.; Fujimoto, N.; Peters, S.; Tsao, A.S.; Mansfield, A.S.; Popat, S.; Jahan, T.; Antonia, S.; et al. First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): A multicentre, randomised, open-label, phase 3 trial. Lancet 2021, 397, 375–386. [Google Scholar] [CrossRef]
- Vellanki, P.J.; Mulkey, F.; Jaigirdar, A.A.; Rodriguez, L.; Wang, Y.; Xu, Y.; Zhao, H.; Liu, J.; Howe, G.; Wang, J.; et al. FDA approval summary: Nivolumab with ipilimumab and chemotherapy for metastatic non–small cell lung cancer, A collaborative project orbis review. Clin. Cancer Res. 2021, 27, 3522–3527. [Google Scholar] [CrossRef]
- Gao, X.; McDermott, D.F. Ipilimumab in combination with nivolumab for the treatment of renal cell carcinoma. Expert Opin. Biol. Ther. 2018, 18, 947–957. [Google Scholar] [CrossRef]
- Sharpe, A.H.; Pauken, K.E. The diverse functions of the PD1 inhibitory pathway. Nat. Rev. Immunol. 2018, 18, 153–167. [Google Scholar] [CrossRef]
- Mallett, G.; Laurence, A.; Amarnath, S. Programmed cell death-1 receptor (Pd-1)-mediated regulation of innate lymphoid cells. Int. J. Mol. Sci. 2019, 20, 2836. [Google Scholar] [CrossRef]
- Upadhaya, S.; Neftelinov, S.T.; Hodge, J.; Campbell, J. Challenges and opportunities in the PD1/PDL1 inhibitor clinical trial landscape. Nat. Rev. Drug Discov. 2022, 21, 482–483. [Google Scholar] [CrossRef]
- Kraehenbuehl, L.; Weng, C.H.; Eghbali, S.; Wolchok, J.D.; Merghoub, T. Enhancing immunotherapy in cancer by targeting emerging immunomodulatory pathways. Nat. Rev. Clin. Oncol. 2022, 19, 37–50. [Google Scholar] [CrossRef]
- Triebel, F.; Jitsukawa, S.; Baixeras, E.; Roman-Roman, S.; Genevee, C.; Viegas-Pequignot, E.; Hercend, T. LAG-3, a novel lymphocyte activation gene closely related to CD4. J. Exp. Med. 1990, 171, 1393–1405. [Google Scholar] [CrossRef]
- Huard, B.; Tournier, M.; Triebel, F. LAG-3 does not define a specific mode of natural killing in human. Immunol. Lett. 1998, 61, 109–112. [Google Scholar] [CrossRef]
- Goldberg, M.V.; Drake, C.G. LAG-3 in cancer immunotherapy. Curr. Top Microbiol. Immunol. 2010, 344, 269–278. [Google Scholar] [CrossRef]
- Shi, A.-P.; Tang, X.-Y.; ** review. Biomed. Pharmacother. 2022, 146, 112512. [Google Scholar] [CrossRef] [PubMed]
- Milone, M.C.; Xu, J.; Chen, S.J.; Collins, M.A.; Zhou, J.; Powell, D.J., Jr.; Melenhorst, J.J. Engineering-enhanced CAR T cells for improved cancer therapy. Nat. Cancer 2021, 2, 780–793. [Google Scholar] [CrossRef]
- Zhang, H.; Gao, L.; Liu, L.; Wang, J.; Wang, S.; Zhang, C.; Liu, Y.; Kong, P.; Liu, J.; He, J.; et al. A Bcma and CD19 Bispecific CAR-T for Relapsed and Refractory Multiple Myeloma. Blood 2019, 134, 3147. [Google Scholar] [CrossRef]
- Kimiz-Gebologlu, I.; Gulce-Iz, S.; Biray-Avci, C. Monoclonal antibodies in cancer immunotherapy. Mol. Biol. Rep. 2018, 45, 2935–2940. [Google Scholar] [CrossRef]
- Simpson, A.; Caballero, O. Monoclonal antibodies for the therapy of cancer. BMC Proc. 2014, 8, O6. [Google Scholar] [CrossRef]
- Zahavi, D.; AlDeghaither, D.; O’Connell, A.; Weiner, L.M. Enhancing antibody-dependent cell-mediated cytotoxicity: A strategy for improving antibody-based immunotherapy. Antib. Ther. 2018, 1, 7–12. [Google Scholar] [CrossRef]
- Bayer, V. An Overview of Monoclonal Antibodies. Semin. Oncol. Nurs. 2019, 35, 150927. [Google Scholar] [CrossRef]
- Kaplon, H.; Reichert, J.M. Antibodies to watch in 2021. mAbs 2021, 13, 1860476. [Google Scholar] [CrossRef] [PubMed]
- **, S.; Sun, Y.; Liang, X.; Gu, X.; Ning, J.; Xu, Y.; Chen, S.; Pan, L. Emerging new therapeutic antibody derivatives for cancer treatment. Signal Transduct. Target. Ther. 2022, 7, 39. [Google Scholar] [CrossRef]
- Taylor, R.P.; Lindorfer, M.A. Cytotoxic mechanisms of immunotherapy: Harnessing complement in the action of anti-tumor monoclonal antibodies. Semin Immunol. 2016, 28, 309–316. [Google Scholar] [CrossRef]
- Golay, J.; Taylor, R. The Role of Complement in the Mechanism of Action of Therapeutic Anti-Cancer mAbs. Antibodies 2020, 9, 58. [Google Scholar] [CrossRef]
- Trivedi, S.; Srivastava, R.M.; Concha-Benavente, F.; Ferrone, S.; Garcia-Bates, T.M.; Li, J.; Ferris, R.L. Anti-EGFR Targeted Monoclonal Antibody Isotype Influences Antitumor Cellular Immunity in Head and Neck Cancer Patients. Clin. Cancer Res. 2016, 22, 5229–5237. [Google Scholar] [CrossRef] [PubMed]
- Boross, P.; Leusen, J.H.W. Mechanisms of action of CD20 antibodies. Am. J. Cancer Res. 2012, 2, 676–690. [Google Scholar]
- Tarantino, P.; Uliano, J.; Morganti, S.; Giugliano, F.; Crimini, E.; Curigliano, G. Clinical development and current role of margetuximab for the treatment of breast cancer. Drugs Today 2021, 57, 551. [Google Scholar] [CrossRef]
- Rajabi, M.; Mousa, S.A. The role of angiogenesis in cancer treatment. Biomedicines 2017, 5, 34. [Google Scholar] [CrossRef] [Green Version]
- Yetkin-Arik, B.; Kastelein, A.W.; Klaassen, I.; Jansen, C.H.J.R.; Latul, Y.P.; Vittori, M.; Biri, A.; Kahraman, K.; Griffioen, A.W.; Amant, F.; et al. Angiogenesis in gynecological cancers and the options for anti-angiogenesis therapy. Biochim. Biophys. Acta Rev. Cancer 2021, 1875, 188446. [Google Scholar] [CrossRef]
- Carmeliet, P. VEGF as a key mediator of angiogenesis in cancer. Oncology 2005, 69, 4–10. [Google Scholar] [CrossRef]
- Salvatore, L.; Bria, E.; Sperduti, I.; Hinke, A.; Hegewisch-Becker, S.; Aparicio, T.; le Malicot, K.; Boige, V.; Koeberle, D.; Baertschi, D.; et al. Bevacizumab as maintenance therapy in patients with metastatic colorectal cancer: A meta-analysis of individual patients’ data from 3 phase III studies. Cancer Treat. Rev. 2021, 97, 102202. [Google Scholar] [CrossRef] [PubMed]
- Oza, A.M.; Dubois, F.; Hegg, R.; Hernández, C.A.; Finocchiaro, G.; Ghiringhelli, F.; Zamagni, C.; Nick, S.; Irahara, N.; Perretti, T.; et al. A Long-Term Extension Study of Bevacizumab in Patients with Solid Tumors. Oncologist 2021, 26, e2254–e2264. [Google Scholar] [CrossRef]
- Reardon, D.A.; Brandes, A.A.; Omuro, A.; Mulholland, P.; Lim, M.; Wick, A.; Baehring, J.; Ahluwalia, M.S.; Roth, P.; Bähr, O.; et al. Effect of Nivolumab vs Bevacizumab in Patients with Recurrent Glioblastoma: The CheckMate 143 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020, 6, 1003–1010. [Google Scholar] [CrossRef] [PubMed]
- Arora, S.; Balasubramaniam, S.; Zhang, H.; Berman, T.; Narayan, P.; Suzman, D.; Bloomquist, E.; Tang, S.; Gong, Y.; Sridhara, R.; et al. FDA Approval Summary: Olaparib Monotherapy or in Combination with Bevacizumab for the Maintenance Treatment of Patients with Advanced Ovarian Cancer. Oncologist 2020, 26, e164–e172. [Google Scholar] [CrossRef] [PubMed]
- Finn, R.S.; Qin, S.; Ikeda, M.; Galle, P.R.; Ducreux, M.; Kim, T.-Y.; Kudo, M.; Breder, V.; Merle, P.; Kaseb, A.O.; et al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N. Engl. J. Med. 2020, 382, 1894–1905. [Google Scholar] [CrossRef] [PubMed]
- Garcia, J.; Hurwitz, H.I.; Sandler, A.B.; Miles, D.; Coleman, R.L.; Deurloo, R.; Chinot, O.L. Bevacizumab (Avastin®) in cancer treatment: A review of 15 years of clinical experience and future outlook. Cancer Treat. Rev. 2020, 86, 102017. [Google Scholar] [CrossRef] [PubMed]
- De Luca, E.; Marino, D.; di Maio, M. Ramucirumab, a second-line option for patients with hepatocellular carcinoma: A review of the evidence. Cancer Manag. Res. 2020, 12, 3721–3729. [Google Scholar] [CrossRef]
- De Vita, F.; Borg, C.; Farina, G.; Geva, R.; Carton, I.; Cuku, H.; Wei, R.; Muro, K. Ramucirumab and paclitaxel in patients with gastric cancer and prior trastuzumab: Subgroup analysis from RAINBOW study. Futur. Oncol. 2019, 15, 2723–2731. [Google Scholar] [CrossRef]
- Uprety, D. Clinical utility of ramucirumab in non-small-cell lung cancer. Biologics 2019, 13, 133–137. [Google Scholar] [CrossRef]
- Bornstein, G.G. Antibody Drug Conjugates: Preclinical Considerations. AAPS J. 2015, 17, 525–534. [Google Scholar] [CrossRef]
- Lucas, A.T.; Moody, A.; Schorzman, A.N.; Zamboni, W.C. Importance and considerations of antibody engineering in antibody-drug conjugates development from a clinical pharmacologist’s perspective. Antibodies 2021, 10, 30. [Google Scholar] [CrossRef]
- Esnault, C.; Schrama, D.; Houben, R.; Guyétant, S.; Desgranges, A.; Martin, C.; Berthon, P.; Viaud-Massuard, M.-C.; Touzé, A.; Kervarrec, T.; et al. Antibody–Drug Conjugates as an Emerging Therapy in Oncodermatology. Cancers 2022, 14, 778. [Google Scholar] [CrossRef]
- Hasan, M.M.; Laws, M.; **, P.; Rahman, K.M. Factors influencing the choice of monoclonal antibodies for antibody–drug conjugates. Drug Discov. Today 2022, 27, 354–361. [Google Scholar] [CrossRef]
- **, Y.; Schladetsch, M.A.; Huang, X.; Balunas, M.J.; Wiemer, A.J. Step** forward in antibody-drug conjugate development. Pharmacol. Ther. 2022, 229, 107917. [Google Scholar] [CrossRef]
- Sheyi, R.; de la Torre, B.G.; Albericio, F. Linkers: An Assurance for Controlled Delivery of Antibody-Drug Conjugate. Pharmaceutics 2022, 14, 396. [Google Scholar] [CrossRef]
- Grzywa, A. Antibody-drug conjugates for cancer therapy. Farm. Polska 2021, 77, 581–587. [Google Scholar] [CrossRef]
- Su, Z.; **: Technology advancements and pitfalls. Ann. Oncol. 2021, 32, 1537–1551. [Google Scholar] [CrossRef] [PubMed]
- Peng, M.; Mo, Y.; Wang, Y.; Wu, P.; Zhang, Y.; **ong, F.; Guo, C.; Wu, X.; Li, Y.; Li, X.; et al. Neoantigen vaccine: An emerging tumor immunotherapy. Mol. Cancer 2019, 18, 128. [Google Scholar] [CrossRef] [PubMed]
- Gopalakrishnan, V.; Helmink, B.A.; Spencer, C.N.; Reuben, A.; Wargo, J.A. The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy. Cancer Cell 2018, 33, 570–580. [Google Scholar] [CrossRef] [PubMed]
- Gopalakrishnan, V.; Spencer, C.N.; Nezi, L.; Reuben, A.; Andrews, M.C.; Karpinets, T.V.; Prieto, P.A.; Vicente, D.; Hoffman, K.; Wei, S.C.; et al. Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients. Science 2018, 359, 97–103. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Disease Condition | Drug Combination | Phase | Participants | Status | NCT Number |
---|---|---|---|---|---|
Non-small cell lung cancer | Durvalumab (anti-PDL1), Oleclumab (anti-CD73), Monalizumab (anti-NKG2A) Durvalumab (anti-PDL1), Domvanalimab (anti-TIGIT) Atezolizumab (anti-PDL1), Pemetrexed, Carboplatin, Cisplatin, Gemcitabine, Paclitaxel | III III III | 999 860 114 | Recruiting Recruiting Recruiting | NCT05221840 NCT05211895 NCT05047250 |
Extensive stage small cell lung cancer | Atezolizumab (anti-PDL1), Chemotherapy (Carboplatin-etoposide) | III | 200 | Not yet recruiting | NCT05468489 |
Metastatic non-small cell lung cancer | Pembrolizumab (anti-PD1), Datopotamab deruxtecan (ADC with TROP2 Ab and Dato-DXd, DS-1062a) Ipilimumab (anti-CTLA-4), Nivolumab (anti-PD1) | III III | 740 265 | Recruiting Active, not recruiting | NCT05215340 NCT03469960 |
Squamous cell non-small cell lung cancer | Sintilimab (anti-PD1), Carboplatin, Albumin-Bound Paclitaxel | III | 236 | Not yet recruiting | NCT05429463 |
Head and Neck squamous cell carcinoma | Monalizumab (anti-NKG2A), Cetuximab (anti-EGFR) | III | 624 | Recruiting | NCT04590963 |
Nasopharyngeal carcinoma | PD-1 antibody, Capecitabine | III | 556 | Recruiting | NCT05342792 |
Gastric cancer | SHR-1701 (bifunctional antibody against PD-L1 and TGF-βRII) | III | 896 | Enrolling by invitation | NCT05149807 |
Colorectal carcinoma | Sintilimab (anti-PD1), Oxaliplatin, Capecitabine | III | 323 | Recruiting | NCT05236972 |
Anal cancer | Sintilimab (anti- PD-1), Chemoradiotherapy | III | 102 | Recruiting | NCT05374252 |
Metastatic urothelial cancer | Avelumab (anti-PDL1), Cabozantinib S-malate | III | 654 | Recruiting | NCT05092958 |
Renal cell carcinoma | Nivolumab (anti-PD1), Tivozanib | III | 326 | Recruiting | NCT04987203 |
Acute myeloid leukemia | Magrolimab (anti-CD47), Venetoclax, Azacitidine | III | 432 | Recruiting | NCT05079230 |
Relapsed or refractory myeloma | Talquetamab (bispecific Ab binding CD3 and GPRC5D), Daratumumab (anti-CD38), Pomalidomide, Dexamethasone | III | 810 | Not yet Recruiting | NCT05455320 |
Recurrent myeloma | Satuximab (anti-CD38), Dexamethasone, Pomalidomide | III | 534 | Recruiting | NCT05405166 |
Melanoma | Fianlimab (anti-LAG3), Cemiplimab (anti-PD1), Pembrolizumab (anti-PD1) Nivolumab (anti-PD1) (subcutaneously versus intravenous), rHuPH20 | III III | 1100 286 | Recruiting Recruiting | NCT05352672 NCT05297565 |
Breast cancer | Inetetamab (anti-HER2), Toripalimab (anti-PD1), Albumin-Bound Paclitaxel | IV | 70 | Not yet Recruiting | NCT05291910 |
Disease Condition | Drug Combinations | Phase | Participants | Status | NCT Number |
---|---|---|---|---|---|
Breast cancer | 4SCAR T cells (CAR-T cells targeting Her2, GD2, and CD44v6) | I/II | 100 | Recruiting | NCT04430595 |
Acute myeloid leukemia | CAR-T CD19 CD7 CAR-T cells | II/III I/II | 10 108 | Recruiting Recruiting | NCT04257175 NCT04599556 |
Multiple myeloma | CAR-T cell targeting B-cell maturation antigen (BCMA), Bortezomib, Dexamethasone, Lenalidomide, Cyclophosphamide, Fludarabine. JNJ-68284528 (cilta-cel), Pomalidomide, Bortezomib, Dexamethasone, Daratumumab JNJ-68284528 (ciltacabtagene autoleucel [cilta-cel], Bortezomib, Lenalidomide, Dexamethasone, Cyclophosphamide, Fludarabine, Daratumumab | III III III | 650 419 750 | Recruiting Active not yet recruiting Not yet recruiting | NCT04923893 NCT04181827 NCT05257083 |
B cell lymphoma | CAR-T-CD19, BTK inhibitor, Fludarabine, Cyclophosphamide | III | 24 | Recruiting | NCT05020392 |
B Cell malignancies | CD19/CD22-CAR-T cells, fludarabine, cyclophosphamide | I/II | 146 | Not yet Recruiting | NCT05442515 |
Solid tumor | CLDN6 CAR-T, CLDN6 RNA-LPX | I/II | 96 | Recruiting | NCT04503278 |
Pancreatic cancer | CD276 CAR-T cells | I/II | 10 | Recruiting | NCT05143151 |
Gastric cancer, Pancreatic cancer | CT041 (CAR-T cells targeting claudin18.2) | I/II | 110 | Recruiting | NCT04404595 |
Prostate cancer | 4SCAR-PSMA T cells [CAR-T cells targeting Prostate-specific membrane antigen (PSMA)] | I/II | 100 | Recruiting | NCT04429451 |
CD44v6 positive cancers (squamous cell carcinomas, adenocarcinomas, melanoma, lymphoma) | 4SCAR-CD44v6 [CAR-T cells targeting CD44v6] | I/II | 100 | Recruiting | NCT04427449 |
Disease Condition | Drug Combination | Phase | Participants | Status | NCT Number |
---|---|---|---|---|---|
Breast cancer | AST-301[pNGVL3-hICD (DNA vaccine against HER2)], rhuGM-CSF, Pembrolizumab Adagloxad simolenin, OBI-821 (Vaccine with tumor-associated antigen Globo H linked to KLH). | II III | 146 668 | Recruiting Recruiting | NCT05163223 NCT03562637 |
Cervical cancer | Recombinant Human Papillomavirus Bivalent Vaccine, Recombinant Human Papillomavirus Nonavalent Vaccine, Diphtheria Toxoid/Tetanus Toxoid/Acellular Pertussis Vaccine Cecolin® (bivalent HPV vaccine) Gardasil® (HPV 9-valent Vaccine) Gardasil-9 (9-valent HPV Vaccination) | IV III III | 5000 1025 1220 | Enrolling by invitation Active, not recruiting Not yet recruiting | NCT05237947 NCT04508309 NCT03848039 |
Colorectal cancer | GRT-C901, GRT-R902[Chimpanzee adenovirus vector (ChAdV)twenty tumor-specific neoantigens (TSNAs)], Atezolizumab, Ipilimumab, Fluoropyrimidine, Bevacizumab, Oxaliplatin | II/III | 665 | Recruiting | NCT05141721 |
Bladder cancer | Bacillus Calmette-Guérin (BCG) Bacillus Calmette Guerin (BCG), PF-06801591(anti-PD1 mAb) | III III | 32 1160 | Active not yet recruiting Recruiting | NCT04806178 NCT04165317 |
Liver cancer | GP96 (Heat Shock Protein-Peptide Complex Vaccine) | II/III | 80 | Not yet Recruiting | NCT04206254 |
Acute myeloid leukemia | DSP-7888 [vaccine with two synthetic peptides derived from Wilms’ tumor 1 (WT1) | II | 100 | Recruiting | NCT04747002 |
Non-small cell lung cancer | UCPVax [vaccine with two peptides from hTERT], Nivolumab | II | 111 | Recruiting | NCT04263051 |
Glioblastoma multiforme | ADCTA-SSI-G1 (Autologous Dendritic Cell/Tumor Antigen) | III | 118 | Recruiting | NCT04277221 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Mishra, A.K.; Ali, A.; Dutta, S.; Banday, S.; Malonia, S.K. Emerging Trends in Immunotherapy for Cancer. Diseases 2022, 10, 60. https://doi.org/10.3390/diseases10030060
Mishra AK, Ali A, Dutta S, Banday S, Malonia SK. Emerging Trends in Immunotherapy for Cancer. Diseases. 2022; 10(3):60. https://doi.org/10.3390/diseases10030060
Chicago/Turabian StyleMishra, Alok K., Amjad Ali, Shubham Dutta, Shahid Banday, and Sunil K. Malonia. 2022. "Emerging Trends in Immunotherapy for Cancer" Diseases 10, no. 3: 60. https://doi.org/10.3390/diseases10030060