Antitumor immunity

McKallip RJ, Nagarkatti M, Nagarkatti PS. Delta-9-tetrahydrocannabinol enhances breast cancer growth and metastasis by suppression of the antitumor immune response. J Immunol 2005 174 3281-9. 

K. Krenek, M. Kuldova, K. Hulfkova, I. Stibor, P. Lhotak, M. Dudic, J. Budka, H. Pelantova, K. Bezouska, A. Fiserova, and V. Kren, /V-Acetyl-D-glucosamine substituted calix[4]arenes as stimulators of NK cell-mediated antitumor immune response, Carbohydr. Res., 342 (2007) 1781-1792. 

Kim TW, Lee TY, Bae HC et al (2007) Oral administration of high molecular mass poly-y-glutamate induces NK cell-mediated antitumor immunity. J Immunol 179 775-780... 

Levitsky, H.I. et al., Immunization with granulocyte-macrophage colony-stimulating factor- transduced, but not B7-l-transduced, lymphoma cells primes idiotype-specific T cells and generates potent systemic antitumor immunity, J Immunol, 156, 3858, 1996. 

Roth A, et al. Induction of effective and antigen-specific antitumor immunity by a liposomal ErbB2/HER2 peptide-based vaccination construct. Br J Cancer. In press. 

To review, in an experimental mouse model, LPDI/E7 vaccination both prevents the establishment of metastatic E7-expressing tumors in naive mice through an induced E7-specific T-cell immune response and, in mice with previously established E7-expressing tumors, causes tumor regression with one subcutaneous injection of LPDI/E7 [Han SJ, et al. Subcutaneous antigen loading of dendritic cells by liposome-protamine-DNA (LPD) nanoparticles results in their activation and induction of specific antitumor immune response (impublished)]. A robust immune response follows administration of LPDI/ peptide particles, which can be used as either a preventative or therapeutic cancer vaccination strategy due to the ability of the particles to prevent and eliminate tumors, respectively, in mouse models. 

Whitmore MM, et al. Systemic administration of LPD prepared with CpG oligonucleotides inhibits the growth of established pulmonary metastases by stimulating innate and acquired antitumor immune responses. Cancer Immunol Immunother 2001 50 503. 

Wang RF, Wang HY. Enhancement of antitumor immunity by prolonging antigen presentation on dendritic cells. Nat Biotechnol 2002 20 149. 

Cytokines have been under clinical investigation as adjuvants to vaccines, and IFNs and IL-2 have shown some positive effects in the response of human subjects to hepatitis vaccine. IL-12 and GM-CSF have also shown adjuvant effects with vaccines. GM-CSF is of particular interest because it promotes recruitment of professional antigen-presenting cells such as the dendritic cells required for priming naive antigen-specific T-lymphocyte responses. There are some claims that GM-CSF can itself stimulate an antitumor immune response, resulting in tumor regression in melanoma and prostate cancer. 

The phase I and phase II trials of therapeutic vaccines (Table 3.) show a weak toxicity of lipids A, furthermore they show a stimulation of the acquired antitumoral immune response. CTL responses correlate better than antibody responses to clinical outcomes, in agreement with current concepts of antitumor immunity. Phase m trials are now necessary to determine the effective protocol. 

The overexpression of HER-2 protein in cancer cells makes it an ideal target for vaccines and other targeting strategies. Vaccines optimized to induce maximum T cell immunity to HER-2 may lead to potent in vivo antitumor immunity. HER-2 protein has been evaluated as a potential target for the development of cancer vaccines because preexistent T cell and antibody responses to HER-2 have been described in breast cancer patients (Disis and Cheever, 1996). In other words, breast cancer patients have preexisting immunity to the HER-2 receptor in the form of elevated antibody titers and T cell immunity. Elevated anti-HER-2 T cell responses have been demonstrated in breast and ovarian cancer patients following immunization with peptides derived from the HER-2 protein (Disis et al., 1999). However, whether peptide-specific T cell responses can be translated to antitumor immunity has yet to be established. 

Mendiratta, S.K., Quezada, A., Matar, M., Wang, J., Hebei, H.L., Long, S., Nordstrom, J.L. and Pericle, F. (1999) Intratumoral delivery of IL-12 gene by polyvinyl polymeric vector system to murine renal and colon carcinoma results in potent antitumor immunity. Gene Ther., 6, 833-839. 

Biragyn, A., Tani, K., Grimm, M.C., Weeks, S. and Kwak, L.W. (1999) Genetic fusion of chemokines to a self tumor antigen induces protective, T-cell dependent antitumor immunity. Nat. Biotechnol, 17, 253-258. 

Chen, C.H., Ji, H., Suh, K.W., Choti, M.A., Pardoll, D.M. and Wu, T.C. (1999) Gene gun-mediated DNA vaccination induces antitumor immunity against human papillomavirus type 16 E7-expressing murine tumor metastases in the liver and lungs. Gene Ther., 6, 1972-1981. 

Ciemik, F., Berzofsky, J.A. and Carbone, D.P. (1996) Induction of cytotoxic T lymphocytes and antitumor immunity with DNA vaccines expressing single T cell epitopes. J. Immunol., 156, 2369-2375. 

Tan, J., Yang, N.S., Turner, J.G., Niu, G.L., Maassab, H.F., Sun, J. etal. (1999) Interleukin-12 cDNA skin transfection potentiates human papillomavirus E6 DNA vaccine-induced antitumor immune response. Cancer Gene Then, 6, 331-339. 

Pervin, S., Chakraborty, M., Bhattacharya-Chatteijee, M., Zeytin, H., Foon, K.A. and Chatterjee, S.K. (1997) Induction of antitumor immunity by an anti-idiotype antibody mimicking carcinoembryonic antigen. Cancer Res., 57, 728-734. 

In addition to the direct cytotoxic effect of PDT on the cells in the tissues and the vasculature targeting there are substantial documentation from in vivo models and some clinical documentation that immunological effects contribute to the therapeutic effect of PDT, in particular for cancer therapy [36-38]. Both attraction of inflammatory cells and other immune reactions have been observed after PDT, but this is beyond the scope of this review. However, the immune response and antitumor immunity induced by PDT as well as PCI of bleomycin has been described in several reviews [39, 40]. 

Many SCLC patients mount an antitumor immune response without signs of PNS [9, 167, 174]. Nevertheless, most SCLC patients do not have this immune response. Thus, the rarity of PNS cannot be attributed to infrequency of antigen expression. This discrepancy suggests that additional factors, perhaps related to tumor major histocompatibility complex (MHC) expression, contribute to the initiation of the PNS immune response. A study of Hu antigen and MHC class I expression in SCLC and neuroblastoma supports this theory. Seventeen of 20 tumors from Hu antibody positive patients expressed both proteins, but only 4 of 30 specimens from seronegative individuals expressed both proteins [171]. Altered expression and/or down-regulation of MHC molecules is a common immune-evasive strategy of tumor cells [175],... 

Entin, I., Plotnikov, A., Korenstein, R. and Keisari, Y. (2003) Tumor growth retardation, cure and induction of antitumor immunity in B16 melanoma bearing mice by low electric field enhanced chemotherapy. Clin. Cancer Res. 9, 3190-3197. 

Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA-4 blockade. Science 1996 271 1734-6. 

Malkovsky M, Dore C, Hunt R et al. (1983) Enhancement of specific antitumor immunity in mice fed a diet enriched in vitamin A acetate. Proc Natl Acad Sci USA 20 6322-6326... 

Willis RA, Bowers WJ, Turner MJ, Fisher TL, Abdul-Ahm CS, Howard DF, Federoff HJ, Lord EM, Erehnger JG (2001) Dendritic cells transduced with HSV-1 amphcons expressing prostate- specific antigen generate antitumor immunity in mice. Hum Gene Ther 12 1867-1879. 

Belardelli Eand Ferrantini M. Cytokines as a link between innate and adaptive antitumor immunity.Trends Immunol 23 201-208, 2002. 

Immunosurveillance and destruction of cancer cells depend on the host immune system, as suggested by recent studies providing direct evidence to the role of cells of the immune system in the inhibition of spontaneous tumor growth [276], T-cell-mediated antitumor immunity was demonstrated in murine tumor models [277-279] as well as in human tumors [280-282]. It is widely accepted that CD4 and CD8 T cells are the major components of this response [283-285], although other cells play important roles in the immunosurveillance against cancer, as the natural killer (NK), NKl.l T (NKT) andy6 T cells [286-288]. 

Clinical studies using molecularly defined MHC class I-restricted antigens and peptides are being conducted in several institutions, and antigen-specific T-cell responses are detected after vaccination. However, the overall immune responses elicited by vaccination with CD8 T-cell peptides are weak and transient. Recently, several studies are demonstrating that to enhance antitumor immunity and eradicate tumor cells in patients, it is necessary to induce both CD4 and CD8" T-cell responses [285,291]. 

Zhou Y, Bosch ML, Salgaller ML (2002) Current methods for loading dendritic cells with tumor antigen for the induction of antitumor immunity. J Immunother 25 289-303... 

Cytokines may have growth inhibitory properties directly on cancer cells, cause tumor regression because of modification of the host tumor relationship, or enhance antitumor immune effects. They may also act as growth factors for malignant cells, and thus therapeutic strategies to inhibit their action become possible. They may also mediate paraneoplastic effects. 

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