Tissue Vaccines for Cancer - 'Whole' Vaccines Might be Better

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Tissue Vaccines for Cancer

Posted 12/13/2007

Mark A Suckow; Heinrich; Elliot D Rosen

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Abstract and Introduction

Abstract

Most tumors, including prostate carcinoma, are heterogeneous mixtures

of neoplastic cells and supporting stromal matrix. Attempts to

vaccinate as a means to treat or prevent cancer have typically relied

on use of a single antigen or cell type. In the case of whole-cell

vaccines, clonal populations of cancer cells are grown in culture and

harvested for vaccine material. However, it is clear from microarray

data that neoplastic cells grown in culture are greatly different from

those found in vivo. Tissue vaccines are harvested directly from

tumors and are used to immunize the animal or the patient. They are

antigenically rich, in that they are comprised of not only neoplastic

cells but also supporting stromal matrix; furthermore, they include

antigens that may be expressed only in vivo and which may be critical

to a successful immune response to the cancer. For these reasons, the

idea that tissue vaccines for cancer have potentially great utility

has merit and should be explored further.

Introduction

Cancer is a group of diseases characterized by uncontrolled growth and

spread of abnormal cells. The clinical outcome of cancer is often

significant debilitation or death. Although great strides have been

made in the clinical approach to cancer, the disease remains a

substantial challenge to clinicians and scientists alike. It is

projected that 1,444,920 new cancer cases will be diagnosed and

559,650 people will die from cancer in the USA in 2007.[1] In this

paper, prostate cancer is given particular focus as a solid tissue

tumor exemplary of many other tumor types.

Cancer of the prostate gland is the most commonly diagnosed cancer in

men and the second most common cancer resulting in death of men, on an

age-adjusted basis.[1] In the majority of cases, prostate carcinoma is

a disease of older men, many of whom have comorbid conditions that

elevate the risk of cancer death.[2-10]

Although the precise mechanisms that lead to the development of

prostate cancer are yet to be defined, it is evident that prostate

cancer develops as the sum result of genetic and epigenetic changes,

including those that inactivate tumor-suppressor genes and activate

oncogenes.[11,12] For example, the inheritance of multiple genetic

factors in humans, such as ELAC2; a gene in the HPC1 region encoding

for 2'-5'-oligoadenylate-dependent ribonuclease L; and a gene within a

region of linkage on chromosome 8 that encodes for macrophage

scavenger receptor, have all been associated with increased risk for

development of prostate cancer.[13-16]

A variety of risk factors have been identified for prostate cancer,

including advancing age, diet, family history and race.[13,17-19] It

is known, for example, that African-American men and black African men

in the UK have increased susceptibilities to the development of the

disease compared with their Caucasian counterparts.[20] Furthermore,

consumption of soy isoflavone-rich diets have been demonstrated to

reduce the incidence of prostate cancer in native Asian men,[21,22]

whereas progeny from east to west developed increasing incidences of

clinical prostate cancer, thereby, linking the change to environmental

factors, possibly related to the change from a soy-based diet.[23,24]

Approximately 20% of all adult human cancers result from chronic

inflammatory processes, presumably triggered by infectious agents or

other environmental factors, and a role for inflammation has also been

recently proposed in prostate carcinogenesis.[25-28]

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