Anti-Tumor Immunity in Head and Neck Cancer: Understanding the Evidence, How Tumors Escape and Immunotherapeutic Approaches
Abstract
:1. Introduction
2. Early Evidence that Deregulated Immunity Plays a Role in HNSCC Progression in Preclinical Models
3. Evidence that the Immune System Limits Formation and Progression of Human HNSCC
4. Immune Escape in Solids Tumors and HNSCC
4.1. Lack of Development of an Anti-Tumor Immune Response
4.2. Suppression of Activated Immune Responses
5. Approaches Utilized to Activate Anti-Tumor Immunity in Patients with HNSCC
5.1. Targeting Immunosuppressive Cells—Myeloid Cells
Drug Category and Name | Mechanism | Combination | Status | Clinical Trial ID | Target Population |
---|---|---|---|---|---|
Checkpoint/ co-stimulatory studies | |||||
Nivolumab | PD1 blocking mAb | single agent | Phase III | NCT02105636 | Recurrent or metastatic HNSCC |
Nivolumab | PD1 blocking mAb with CD27 agonist mAb | with Varlilumab | Phase I/II | NCT02335918 | Advanced solid tumors |
Nivolumab | PD1 blocking mAb with IDO1 inhibitor | with INCB24360 | Phase I/II | NCT02327078 | Advanced solid tumors |
Nivolumab | PD1 blocking mAb with CSF1R blocking mAb | with PLX3397 | Phase I | NCT02526017 | Advanced solid tumors |
Nivolumab | PD1 blocking mAb | single agent | Phase I/II | NCT02488759 | Advanced and metastatic HPC-associated HNSCC |
Pembrolizumab | PD1 blocking mAb with Bruton’s TKI | with ACP-196 | Phase II | NCT02454179 | Advanced HNSCC |
Pembrolizumab | Head to head comparison | vs. standard treatment (docetaxel/methotrexate/cetixumab) | Phase III | NCT02252042 | Recurrent or metastatic HNSCC |
Pembrolizumab | Head to head comparison | Pembro+standard treament vs. cetiximab+standard treatment | Phase III | NCT02358031 | Recurrent or metastatic HNSCC |
Pembrolizumab | PD1 blocking mAb | single agent | Phase II | NCT02255097 | Recurrent or metastatic HNSCC after CDDP/cetixumab failure |
Pembrolizumab | PD1 blocking mAb with IDO1 inhibitor | with INCB024360 | Phase I/II | NCT02178722 | Advanced or recurrent solid tumors |
Pembrolizumab | PD1 blocking mAb with CSF1R blocking mAb | with PLX3397 | Phase I/II | NCT02452424 | Advanced solid tumors |
Pembrolizumab | PD1 blocking mAb | single agent, window-of-opportunity trial before surgery | Phase II | NCT02296684 | Advanced but resectable HNSCC |
Pembrolizumab | PD1 blocking mAb with B7-H3 blocking mAb | with MGA271 | Phase I | NCT02475213 | B7-H3+ advanced HNSCC |
PF-05082566 | 41BB agonist mAb with PD1 blocking mAb | with Pembrolizumab | Phase I | NCT02179918 | Advanced solid tumors |
Urelumab | 41BB agonist mAb with EGFR targeting mAb | with cetuximab | Phase I | NCT02110082 | Advanced/metastatic HNSCC |
MEDI4736 | PD-L1 blocking mAb with CTLA4 blocking mAb | with or without tremelimumab | Phase III | NCT02369874 | Recurrent or metastatic HNSCC |
MEDI4736 | PD-L1 blocking mAb with STAT3 inhibitor or CXCR2 blocking mAb | with AZD9150 or AZD5069 | Phase I/II | NCT02499328 | Metastatic HNSCC |
MEDI4736 | PD-L1 blocking mAb | single agent | Phase II | NCT02207530 | Recurrent or metastatic HNSCC |
MEDI4736 | PD-L1 blocking mAb with HPV E7 expressing Listeria vector | with ADXS 11-001 | Phase I/II | NCT02291055 | Recurrent or metastatic HPV-associated HNSCC |
MEDI4736 | PD-L1 blocking mAb with CCR4 blocking mAb | with mogamulizumab | Phase I | NCT02301130 | Advanced solid tumors |
Tremelimumab | CTLA4 blocking mAb with CCR4 blocking mAb | with mogamulizumab | Phase I | NCT02301130 | Advanced solid tumors |
Ipilimumab | CTLA4 blocking mAb | with cetiximab and XRT | Phase I | NCT01935921 | Advanced HNSCC |
Ipilimumab | CTLA4 blocking mAb with B7-H3 blocking mAb | with MGA271 | Phase I | NCT02381314 | B7-H3+ advanced HNSCC |
PF04518600 | OX40 agonist mAb | single agent | Phase I | NCT02315066 | Recurrent or metastatic HNSCC |
MDSC targeting trials | |||||
Tadalafil | PDE5 inhibitor | single agent | Phase II | NCT01697800 | All stage HNSCC |
Therapeutic Vaccines | |||||
VGX-3100 and INO-9012 | HPV DNA vaccine | single agent, delivered via IM electroporation, both surgery and CRT arms | Phase I/II | NCT02163057 | HPV-associated HNSCC |
ADXS 11-001 | HPV E7 expressing Listeria vector | with or without αPD-L1 mAb (MEDI4736) | Phase I/II | NCT02291055 | HPV-associated HNSCC |
ADXS 11-001 | HPV E7 expressing Listeria vector | single agent, window-of-opportunity trial before surgery | Phase II | NCT02002182 | Stage II-IV resectable HPV-associated OPSCC |
CDDP plus VICORYX-2 | p16 peptide antigen | with or without Montanide® ISA-51 VG (adjuvant) | Phase I | NCT02526316 | HPV-associated HNSCC (p16+) |
AlloVax | Whole tumor cell lysate vaccine | with AlloStim adjuvant | Phase I/II | NCT01998542 | Metastatic or recurrent HNSCC |
Adoptive T Cell Transfer | |||||
Adoptive cell transfer | Ex-vivo TIL expansion with adoptive transfer | combined with lymphodepletion | Phase II | NCT01585428 | Metastatic HPV-associated OPSCC |
Adoptive cell transfer | Ex-vivo TIL expansion after genetic modification with adoptive transfer | combined with lymphodepletion, viral insertion of a HPV-specific TCR | Phase I/II | NCT02280811 | All HPV-associated cancer |
Cetuximab-based trials | |||||
Cetixumab | EGFR targeting mAb with standard treatments | with XRT and paclitaxel-poliglumex | Phase I/II | NCT00660218 | HPV-negative advanced HNSCC |
Cetixumab | EGFR targeting mAb with XRT | XRT | Phase II | NCT00904345 | Advanced HNSCC |
Cetixumab | EGFR targeting mAb with αCTLA4 mAb with XRT | Ipilumimab and XRT | Phase I | NCT01935921 | Advanced HNSCC |
Cetixumab | Head to head comparison | cetixumab plus XRT vs. CDDP plus XRT | Phase III | NCT01855451 | HPV-associated HNSCC |
Cetixumab | EGFR targeting mAb with cyclin D inhibitor | with PD0332991 | Phase I/II | NCT02101034 | Incurable HNSCC |
Cetixumab | Head to head comparison | cetuximab vs. MEHD7945A | Phase II | NCT01577173 | Metastatic or recurrent HNSCC |
Cetixumab | EGFR targeting mAb with TLR8 agonist | with VTX-2337, window-of-opportunity trial before surgery | Phase I | NCT02124850 | resectable HNSCC |
Cetixumab | EGFR targeting mAb with TLR8 agonist and chemotherapy | with VTX-2337 and CDDP+5-FU | Phase II | NCT01836029 | Recurrent or metastatic HNSCC |
5.2. Targeting Immunosuppressive Cells—Tregs
5.3. Therapeutic Tumor Vaccines
5.4. Ex Vivo Immune Cell Priming with Adoptive Transfer
5.5. Targeting Cancer Cells with Monoclonal Antibodies
5.6. Therapeutic Antibody Checkpoint Inhibition and Co-Stimulatory Agonists
6. Conclusions and Future Directions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Allen, C.T.; Clavijo, P.E.; Van Waes, C.; Chen, Z. Anti-Tumor Immunity in Head and Neck Cancer: Understanding the Evidence, How Tumors Escape and Immunotherapeutic Approaches. Cancers 2015, 7, 2397-2414. https://doi.org/10.3390/cancers7040900
Allen CT, Clavijo PE, Van Waes C, Chen Z. Anti-Tumor Immunity in Head and Neck Cancer: Understanding the Evidence, How Tumors Escape and Immunotherapeutic Approaches. Cancers. 2015; 7(4):2397-2414. https://doi.org/10.3390/cancers7040900
Chicago/Turabian StyleAllen, Clint T., Paul E. Clavijo, Carter Van Waes, and Zhong Chen. 2015. "Anti-Tumor Immunity in Head and Neck Cancer: Understanding the Evidence, How Tumors Escape and Immunotherapeutic Approaches" Cancers 7, no. 4: 2397-2414. https://doi.org/10.3390/cancers7040900