Biomarkers for immunostimulatory monoclonal antibodies in combination strategies for melanoma and other tumor types Journal Article
| Authors: | Ascierto, P. A.; Kalos, M.; Schaer, D. A.; Callahan, M. K.; Wolchok, J. D. |
| Article Title: | Biomarkers for immunostimulatory monoclonal antibodies in combination strategies for melanoma and other tumor types |
| Abstract: | Modulation of the immune system by targeting coinhibitory and costimulatory receptors has become a promising newapproach of immunotherapy for cancer. The recent approval of the CTLA-4-blocking antibody ipilimumab for the treatment of melanoma was a watershed event, opening up a new era in the field of immunotherapy. Ipilimumab was the first treatment to ever show enhanced overall survival (OS) for patients with stage IVmelanoma. However, measuring response rates using standard Response Evaluation Criteria in Solid Tumors (RECIST) or modified World Health Organization criteria or progression-free survival does not accurately capture the potential for clinical benefit for ipilimumab-treated patients. As immunotherapy approaches are translated into more tumor types, it is important to study biomarkers, which may be more predictive of OS to identify the patients most likely to have clinical benefit. Ipilimumab is the first-in-class of a series of immunomodulating antibodies that are in clinical development. Anti-PD1 (nivolumab and MK-3475), anti-PD-L1 (BMS-936 559, RG7446, and MEDI4736), anti-CD137 (urelumab), anti-OX40, anti- GITR, and anti-CD40 monoclonal antibodies are just some of the agents that are being actively investigated in clinical trials, each having the potential for combination with the ipilimumab to enhance its effectiveness. Development of rational combinations of immunomodulatory antibodies with small-molecule pathway inhibitor therapies such as vemurafenib makes the discovery of predictive biomarkers even more important. Identifying reliable biomarkers is a necessary step in personalizing the treatment of each patient's cancer through a baseline assessment of tumor gene expression and/or immune profile to optimize therapy for the best chance of therapeutic success. © 2012 American Association for Cancer Research. |
| Keywords: | overall survival; cancer recurrence; placebo; nonhuman; unspecified side effect; paclitaxel; pancreas cancer; temozolomide; cancer staging; drug megadose; neoplasms; transcription factor foxp3; cd8+ t lymphocyte; t lymphocyte; tumor associated leukocyte; c reactive protein; biological markers; carboplatin; dacarbazine; interleukin 2; ipilimumab; ticilimumab; cancer immunotherapy; melanoma; progression free survival; dendritic cell; lung cancer; monoclonal antibody; prostate cancer; regulatory t lymphocyte; antibodies, monoclonal; hematologic malignancy; cancer vaccines; melanoma antigen 3; ny eso 1 antigen; adoptive transfer; disease free interval; immunomodulation; lactate dehydrogenase; leukocyte count; immunologic factors; kidney cancer; lymphocytic infiltration; cytotoxic t lymphocyte antigen 4; humoral immunity; t lymphocyte activation; immunopathology; lymphocyte count; suppressor cell; inducible t cell costimulator; immunization; programmed death 1 ligand 1; programmed death 1 receptor; fotemustine; metastatic melanoma; tumor microenvironment; melanoma vaccine; denileukin diftitox; individualized medicine; vemurafenib; sipuleucel t; cancer prognosis; dabrafenib; long term survival; nivolumab; talimogene laherparepvec |
| Journal Title: | Clinical Cancer Research |
| Volume: | 19 |
| Issue: | 5 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2013-03-01 |
| Start Page: | 1009 |
| End Page: | 1020 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-12-2982 |
| PROVIDER: | scopus |
| PUBMED: | 23460532 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 3" - "Export Date: 1 April 2013" - "CODEN: CCREF" - "Source: Scopus" |
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