Leveraging the Activity of Tumor Vaccines with Cytotoxic Chemotherapy

Abstract

Engaging the power of the patient's own immune system to actively seek out and destroy transformed cells holds great promise for cancer therapy. Tumor vaccines offer the potential for preventing cancer in high-risk individuals, preventing disease relapse after diagnosis and initial therapy, and shifting the balance of the host-tumor interaction to mitigate the progression of advanced cancers. The therapeutic activity of tumor vaccines is limited by the sheer physical burden of the cancer itself, pathways of local immune tolerance and escape active within the tumor microenvironment, and superimposed potent systemic mechanisms of immune tolerance. In this review, we describe how cytotoxic chemotherapy can be integrated with tumor vaccines using unique doses and schedules to break down these barriers, releasing the full potential of the antitumor immune response to eradicate disease. (Cancer Res 2005; 65(18): 8059-64)

Experience of more than 100 preimplantation genetic diagnosis cycles for monogenetic diseases using whole genome amplification and linkage analysis in a single centre

“…Other known risk factors involved in breast cancer include obesity, use of hormone therapies (progestin and oestrogen), increased breast tissue density, alcohol use, and physical inactivity. 17 In 2003, the ESHRE Ethics Task Force published a recommended multidisciplinary approach to the application of PGD, stating that PGD for multifactorial diseases such as BRCA mutation is acceptable notwithstanding the uncertainties about the genetic predisposition and the epigenetic influence. 18 The United Kingdom Human Fertilisation and Embryology Authority also accepted PGD for various hereditary cancer syndromes, including familial adenomatous polyposis, neurofibromatosis type 1 and type 2, and von Hippel-Lindau syndrome.…”

Cancer Stem Cells: A Review of Potential Clinical Applications

“…Future studies of CSCs and expression of CTAs, as well as other tumor-specific antigens, may not only shed additional light on the biology of cancer but also may lead to the development of synergistic strategies in battling minimal residual disease, such as immunotherapeutic approaches targeting CTAs. 55 …”

The anti-apoptotic members of the Bcl-2 family are attractive tumor-associated antigens

“…However, recent data from the clinic suggests a synergistic effect of anti-cancer vaccines and chemotherapy. As an example hereof, the combination of immunotherapy with high-dose chemotherapy has been described to improve the severe immunodeficiency and leave to the induction of clinically relevant immunity in myeloma patients [51]. Notably, lympho-ablation, e.g.…”

“…Rational treatment strategies that combine tumor vaccines with cytotoxic drugs can be integrated in at least three ways as suggested by Emens and Jaffee [51]. First, chemotherapeutics can be combined with surgery and radiation to achieve a state of minimal residual disease, thereby altering the balance of the disease burden and the vaccine-induced T-cell response in favour of the T cell.…”