Publications by authors named "James Lee Murray"

4 Publications

  • Page 1 of 1

Developing anti-HER2 vaccines: Breast cancer experience.

Int J Cancer 2018 11 10;143(9):2126-2132. Epub 2018 May 10.

Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.

Breast cancer accounts for more than one million new cases annually and is the leading cause of death in women globally. HER2 overexpression induces cellular and humoral immune responses against the HER2 protein and is associated with higher tumor proliferation rates. Trastuzumab-based therapies are effectively and widely used as standard of care in HER2-amplified/overexpressed breast cancer patients; one cited mechanism of action is the induction of passive immunity and antibody-dependent cellular cytotoxicity against malignant breast cancer cells. These findings drove the efforts to generate antigen-specific immunotherapy to trigger the patient's immune system to target HER2-overexpressing tumor cells, which led to the development of various vaccines against the HER2 antigen. This article discusses the various anti-HER2 vaccine formulations and strategies and their potential role in the metastatic and adjuvant settings.
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http://dx.doi.org/10.1002/ijc.31551DOI Listing
November 2018

Randomized phase II trial of letrozole plus anti-MUC1 antibody AS1402 in hormone receptor-positive locally advanced or metastatic breast cancer.

Clin Cancer Res 2011 Nov 30;17(21):6822-30. Epub 2011 Aug 30.

Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.

Purpose: AS1402 is a humanized immunoglobulin G1 antibody that targets the aberrantly glycosylated antigen MUC1, which is overexpressed in 90% of breast tumors and contributes to estrogen-mediated growth and survival of breast cancer cells in vitro by modulating estrogen receptor (ER) activity. Aromatase inhibitors have been reported to enhance antibody-dependent cell-mediated cytotoxicity elicited by antibodies in vitro. We compared the outcomes of patients with breast cancer treated with letrozole with or without AS1402.

Experimental Design: The study population included 110 patients with locally advanced or metastatic hormone receptor-positive breast cancer randomized to receive 2.5 mg letrozole only once daily or with a weekly 9 mg/kg AS1402 infusion. The primary endpoint was overall response rate. Secondary endpoints included progression-free survival, time to progression, and safety. AS1402 exposure and influence of allotypes of FcγRIIIa, FcγRIIa, and MUC1 were evaluated.

Results: The study was stopped early because of a trend toward worse response rates and a higher rate of early disease progression in the AS1402 + letrozole arm. Final analysis revealed no significant difference in efficacy between the study arms. Evaluated gene polymorphisms did not define patient subgroups with improved outcomes. Addition of AS1402 to letrozole was associated with manageable toxicity.

Conclusions: Because adding AS1402 to letrozole did not improve outcomes compared with letrozole only, blocking ER may be a better strategy for harnessing MUC1 modulation of the ER to a clinical advantage. FcγRIIIa, FcγRIIa, and MUC1 allotype did not predict outcome for patients treated with letrozole with or without AS1402.
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http://dx.doi.org/10.1158/1078-0432.CCR-11-1151DOI Listing
November 2011

Phase III multicenter clinical trial of the sialyl-TN (STn)-keyhole limpet hemocyanin (KLH) vaccine for metastatic breast cancer.

Oncologist 2011 14;16(8):1092-100. Epub 2011 May 14.

Mount Vernon Cancer Center, Northwood, Middlesex, United Kingdom.

Purpose: This double-blind, randomized, phase III clinical trial evaluated time to progression (TTP) and overall survival in women with metastatic breast cancer (MBC) who received sialyl-TN (STn) keyhole limpet hemocyanin (KLH) vaccine. Secondary endpoints included vaccine safety and immune response.

Experimental Design: The study population consisted of 1,028 women with MBC across 126 centers who had previously received chemotherapy and had had either a complete or a partial response or no disease progression. All women received one-time i.v. cyclophosphamide (300 mg/m(2)) 3 days before s.c. injection of 100 μg STn-KLH plus adjuvant (treatment group) or 100 μg KLH plus adjuvant (control group) at weeks 0, 2, 5, and 9. Subsequently, STn-KLH without adjuvant or KLH without adjuvant was then administered monthly for 4 months, and then quarterly until disease progression, without cyclophosphamide.

Results: STn-KLH vaccine was well tolerated; patients had mild to moderate injection-site reactions and reversible flu-like symptoms. Week-12 antibody testing revealed high specific IgG titers and a high rate of IgM-to-IgG seroconversion; the median IgG titers in STn-KLH recipients were 320 (anti-ovine submaxillary mucin) and 20,480 (anti-STn), with no detectable antimucin antibodies in the control group. The TTP was 3.4 months in the treatment group and 3.0 months in the control group. The median survival times were 23.1 months and 22.3 months, respectively.

Conclusions: Although STn-KLH was well tolerated in this largest to date metastatic breast cancer vaccine trial, no overall benefit in TTP or survival was observed. Lessons were learned for future vaccine study designs.
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http://dx.doi.org/10.1634/theoncologist.2010-0307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3228158PMC
February 2012

Clinical development of the STn-KLH vaccine (Theratope).

Clin Breast Cancer 2003 Feb;3 Suppl 4:S139-43

Department of Breast Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030-4009, USA.

The development of active specific immunotherapy depends on the identification of altered cancer cell-specific molecules or epitopes that are immunogenic. Many cancer-specific peptide or glycoprotein target antigens have been identified. Tumors carrying aberrant epitopes as a result of underglycosylation of mucins are associated with poor prognosis in many epithelial cancers. The aberrant mucin sialyl-Tn (STn) epitope, in addition to being a predictor of poor prognosis when expressed in tumors, is associated with increased aggressiveness and metastatic potential, making it a promising target for immunotherapy. The STn-keyhole limpet hemocyanin (KLH) vaccine (Theratope) is an investigational active specific immunotherapy consisting of a synthetic STn epitope conjugated to a high molecular weight protein carrier, KLH. The immune response generated by the STn-KLH vaccine is both humoral and cellular. More than 1000 breast cancer patients with metastatic disease are currently enrolled in a phase III clinical trial to assess the safety and efficacy of the STn-KLH vaccine. Interim analysis from a current phase III trial has confirmed the safety of the STn-KLH vaccine, and the clinical outcome awaits the final analysis expected in 2003.
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http://dx.doi.org/10.3816/cbc.2003.s.003DOI Listing
February 2003