HLA class I antigen loss, tumor immune escape and immune selection

Campoli, Michael; Chang, Chien‐Chung; Ferrone, Soldano

doi:10.1016/s0264-410x(02)00386-9

Cited by 110 publications

(75 citation statements)

References 16 publications

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“…However, other mechanisms responsible for tumor escape might be involved as it has been suggested in the literature, which might also have a role in the escape of HER2/neuoverexpressing tumors. Among these, downregulation of MHC class I cell surface expression 24,25 and/or of intercellular adhesion molecule 1, which is involved in homing of cytolytic effector T cells into the tumors, 26 have been reported in many solid tumors. Future studies will focus on the delineation of the role of these escape mechanisms and other factors such as the presence of suppressive immune cells in these slow-growing tumors.…”

Section: Discussionmentioning

confidence: 99%

Development of a live and highly attenuated Listeria monocytogenes-based vaccine for the treatment of Her2/neu-overexpressing cancers in human

et al. 2010

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A chimeric human Her2/neu gene (ChHer2) harboring most of the known major histocompatibility complex class I epitopes of the HER2/neu oncogene was expressed as a fusion protein to a non-hemolytic fragment of listeriolysin O (LLO), by the highly attenuated Listeria vector LmddA, which lacks antibiotic selection markers and the ability to spread from cell-to-cell. This construct (ADXS31-164) was tested for immunogenicity and anti-tumor effects in mice. Despite being highly attenuated, ADXS31-164 proved to be efficacious in breaking immune tolerance toward the HER2/neu self-antigen. ADXS31-164 elicited strong T-cell immune responses in experimental animals. In tumors, ADXS31-164 caused a reduction in regulatory T cells (Treg) accompanied by an increase in the CD8 þ /Treg ratio. Comparison of this vaccine with the conventional antibiotic resistant Listeria vector (Lm-LLO-ChHer2) shows that ADXS31-164 is more efficacious in delaying tumor growth in Her2/neu transgenic animals. Because of its well-defined attenuation mechanism and independence from antibiotic selection markers, ADXS31-164 is potentially more suitable for human use. These results support the future clinical development of this vaccine for the treatment of HER2/neuoverexpressing malignancies, such as breast, colorectal and pancreatic cancers.

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Section: Discussionmentioning

confidence: 99%

Development of a live and highly attenuated Listeria monocytogenes-based vaccine for the treatment of Her2/neu-overexpressing cancers in human

et al. 2010

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“…This discrepancy has in numerous cases been explained by immune escape mechanisms of the tumor cells. 47 For therapeutic strategies targeting antigens that play an insignificant role in cancer growth, the selection of antigen deficient cancer cells is a well-recognized limitation. 48,49 Thus, the attractiveness of using survivin as a target for vaccination relies on the fact that immune escape by down regulation or loss of expression of this protein would impair sustained tumor growth.…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Survivin-Derived CTL Epitopes with Different HLA-A-Restriction Profiles

Reker

Meier

Holten-Andersen

et al. 2004

Cancer Biology & Therapy

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The identification of tumor antigens, which are essential for the survival of tumor cells is a new avenue to prevent antigen loss variants emerging due to immunoselection, particularly during immune therapy. In the search for such immunogenic tumor antigens, we recently identified spontaneous cytotoxic lymphocyte (CTL) responses against the inhibitor of apoptosis protein survivin. Thus, we identified two HLA-A2-restricted, survivin-derived CTL epitopes, which both were targets for spontaneous CTL responses in melanoma, breast cancer, and CLL. Here, we extend these data and describe the characterization of novel HLA-A1-, HLA-A2-, HLA-A3-, and HLA-A11-restricted survivin epitopes on the basis of spontaneous CTL responses in cancer patients. These epitopes significantly increase the number of patients eligible for immunotherapy based on survivin derived peptides. Additionally, the collective targeting of several restriction elements is likely to decrease the risk of immune escape by HLA-allele loss.

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“…The characterization of multiple Mcl-1 epitopes with different HLA class I restriction elements broadens the clinical potential of this target antigen in several important ways: Targeting different HLA molecules in a multiepitope vaccine will increase the number of patients eligible for immunotherapy and will further decrease the risk of immune escape by class I HLA-allele loss; loss of a single class I HLA allele is a significant component of MHC alterations described in cancer cells, whereas total loss of class I HLA expression is rare. 5 The attractiveness of using Mcl-1 for vaccination purposes relies on the fact that downregulation or loss of expression of this protein as a means of immune escape would impair sustained tumor growth. The availability of multiple Mcl-1 epitopes presented by different HLA class I restriction elements further reduces the risk of immune escape and thereby therapeutic failures.…”

Section: To the Editormentioning

confidence: 99%

“…Interestingly, serine protease inhibitors even promoted cell death in imatinibtreated cells. 5 Authors concluded that imatinib mesylate induced a caspase-independent, necrosis-like PCD mediated by the serine protease activity of Omi/HtrA2. 5 Their experiments were mainly…”

Section: To the Editormentioning

confidence: 99%