Vaccine-induced antibody responses in patients with carcinoma

Abstract

Cancer vaccines based on defined antigens are capable of inducing antibodies that recognize and kill tumor cells. Antibodies are ideally suited to address minimal residual disease, and vaccination in an adjuvant setting may favorably influence the outcome of a disease. The present article gives a short summary of antibody production by B cells, and the mechanism of action of antibodies, as well as a description of the current methods for measuring antibody responses and for assessing their antitumor efficacy in the context of clinical trials. It concludes with an overview of antibody responses induced by vaccines based on structurally defined tumor-associated antigens tested in patients with carcinomas. Correlation between antibody responses, T-cell responses and clinical outcome has been noted in a few studies, signaling the importance of vaccine design and adjuvants to exploit the interactions of the innate and adaptive immune system. However, humoral responses, which may provide a surrogate marker for T-helper responses and simplify monitoring of large Phase III trials, are still not or incompletely explored in many vaccination trials.

Keywords::

• antibody
• antibody-dependent cellular cytotoxicity
• cancer
• clinical trial
• complement-dependent cytotoxicity
• ELISA
• tumor-associated antigen
• vaccine

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Notes

mAb: Monoclonal antibody; TAA: Tumor-associated antigen.

^†Serum levels of these antigens are measured in the clinic with commercial assays and are used to monitor response to treatment and progression in breast cancer (MUC1/cancer antigen 15.3) [168], in ovarian cancer (MUC16/cancer antigen 125) [169] and in gastrointestinal malignancies (sialyl Lewis A/cancer antigen 19.9) [170]. Carcinoembryonic antigen is used in a number of carcinomas for the same purposes [171]. In addition to monitoring, prostate-specific antigen is used for screening for prostate cancer [172].

MUC: Mucin.

ADCC: Antibody-dependent cellular cytotoxicity; CDC: Complement-dependent cytotoxicity; SEREX: Serological analysis of recombinant cDNA expression libraries.