Tumor stroma-associated antigens for anti-cancer immunotherapy

Abstract

Immunotherapy has been widely investigated for its potential use in cancer therapy and it becomes more and more apparent that the selection of target antigens is essential for its efficacy. Indeed, limited clinical efficacy is partly due to immune evasion mechanisms of neoplastic cells, e.g. downregulation of expression or presentation of the respective antigens. Consequently, antigens contributing to tumor cell survival seem to be more suitable therapeutic targets. However, even such antigens may be subject to immune evasion due to impaired processing and cell surface expression. Since development and progression of tumors is not only dependent on cancer cells themselves but also on the active contribution of the stromal cells, e.g. by secreting growth supporting factors, enzymes degrading the extracellular matrix or angiogenic factors, the tumor stroma may also serve as a target for immune intervention. To this end several antigens have been identified which are induced or upregulated on the tumor stroma. Tumor stroma-associated antigens are characterized by an otherwise restricted expression pattern, particularly with respect to differentiated tissues, and they have been successfully targeted by passive and active immunotherapy in preclinical models. Moreover, some of these strategies have already been translated into clinical trials.

Laryngeal carcinoma prognosis after postoperative radiotherapy correlates with CD105 expression, but not with angiogenin or EGFR expression

“…The evidence that antibodies against CD105 reacted preferentially with active endothelial cells of angiogenic tissues [22] could be extremely useful for the purposes of vascular targeting. Immunotherapy using antibodies specific for CD105, alone or conjugated with different effector molecules, has been shown to bind specifically to proliferating endothelial cells in preclinical models, rapidly accumulating in tumors [23,24]. In particular, anti-CD105 monoclonal antibodies have proved effective in inhibiting tumor angiogenesis, growth and metastasis in animal models [25].…”

Multipeptide vaccination in cancer patients

“…In fact, the targeting of multiple Ags, which include epitopes deriving from endothelia and stromal cell proteins, may offer a supplementary benefit, related to the possibility of also targetting tissues that are non neoplastic by themselves, but participate in sustaining the neoplastic process [31]. Indeed, increasing evidence has highlighted the tight interconnection between cancer cells and tumor stroma in tumor development and growth, with the stroma supplying cancer cells with growth factors, proteolytic enzymes and angiogenic and immunosuppressive factors.…”

Harnessing the Immune System to Fight Cancer: The Promise of Genetic Cancer Vaccines

“…In contrast to cancer cells, tumour stroma cells are genetically more stable so that at least some immune evasion mechanisms of tumours do not apply to these cells. Nevertheless, stroma cells differ from their normal counterparts by upregulation or induction of various antigens (reviewed in Hofmeister et al, 2006). Some of the tumour stroma-associated antigens (TSAAs) are highly selective for the tumour microenvironment.…”