Augmenting the Potency of Breast Cancer Vaccines: Combined Modality Immunotherapy

Issue title: Immunology of Breast Cancer

Guest editors: Wei-Zen Weix and Diana Lopezy

Article type: Research Article

Authors: Emens, Leisha A.^{a; *} | Reilly, R. Todd^a | Jaffee, Elizabeth M.^{a; b; c; d}

Affiliations: [a] Department of Oncology, The Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA | [b] Department of Immunology, The Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA | [c] Department of Pathology, The Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA | [d] Department of Pharmacology, The Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA | [x] Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA | [y] Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, FL 33136, USA

Correspondence: [*] Corresponding author: Leisha A. Emens, M.D., Ph.D., Assistant Professor of Oncology, The Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Bunting-Blaustein Cancer Research Building, 1650 Orleans Street, Room 4M90, Baltimore, MD 21231-1000, USA. Tel.: +1 410 502 7051; Fax: +1 410 614 8216; E-mail: emensle@jhmi.edu

Abstract: Rapid progress in defining the molecular underpinnings of the antitumor immune response has laid the foundation for tumor immunotherapy, leading to multiple early clinical studies testing vaccines for the treatment of breast cancer. Together, these small trials have provided early evidence for the induction of clinically relevant vaccine-induced tumor-specific immunity in some patients. However, they have not convincingly demonstrated a significant impact on disease progression or overall survival in women with advanced breast cancer. These disappointing results are likely due to the negative impact of standard cancer treatments on vaccine-activated antitumor immunity, the limited potency of current tumor vaccine formulations against large burdens of established tumor, and the presence of pre-existing tumor-specific immune tolerance. It is increasingly clear that standard and novel breast cancer treatments can influence the antitumor immune response. Also, signaling pathways that regulate immune responses have emerged as novel targets for immune modulation. The use of preclinical models to elucidate the pharmacodynamic interactions of standard breast cancer treatment modalities and novel, targeted immunotherapeutics with breast cancer vaccines will facilitate the development of combinatorial immunotherapeutic strategies. Combined modality immunotherapies should maximize the potency of the antitumor immune response, thereby improving the outcome of breast cancer therapy.

DOI: 10.3233/BD-2004-20103

Journal: Breast Disease, vol. 20, no. 1, pp. 13-24, 2004