Tumors cellular immune response

CpG ODNs are also effective as vaccine adjuvants to enhance adaptive TH1 cellular immune responses.104 In mice, CpG ODNs can trigger strong TH1 responses,105 enhancing the number and function of tumor-specific Cytotoxic T lymphocytes (CTLs) and IFN-y secreting T cells.106 This has resulted in therapeutic vaccines in mouse tumor models where no other approach has shown comparable efficacy, even with large (1 cm) established tumors.107 108 Even without a vaccine, CpG ODNs can induce CD8+ T cell-mediated regression of established tumors with durable memory responses.109... 

In addition to monoclonal antibody or chemotherapy, immunotherapy has been developed to target tumor antigen for the treatment of FL. The unique sequence of the protein, so-called idiotype (Id) protein, can be a target of immunotherapy. Because Id protein can induce humoral and cellular immune responses against idiotype protein, vaccination with Id protein can decrease the risk of progression. However, the mechanism of anti-Id response has been unclear. 

The resistance of many human cancers to immunotherapies has been attributed to the presence of immunosuppressive molecules located in tumor areas. Adenosine is present at elevated levels in hypoxic tissues due to an increased intracellular production and extracellular accumulation, as described above. This nucleoside activates cell surface receptors on T and NK cells that mediate cellular immune responses to tumor cells. It is well established that T cells recognize and destroy... 

Bispecific monoclonal antibodies are artificially developed antibodies with antigenbinding sites physically linked to different specificities. It is thought that bispecific monoclonal antibodies activate the cellular immune response by crosslinking immune cells to tumor cells, thus circumventing the proper structures for tumor cell-immune cell interactions (Koelemij et al., 1999). These antibodies are effective in low concentrations in vivo. For example, Kufer et al. (1996) have combined the anti-CD3 specificity directed against T cells in a bispecific monoclonal antibody, with the specificity against the tumor-associated 17-1A antigen. This antibody could be a major improvement, for example, in the therapy for disseminated micrometastatic tumor cells. 

Mechanism of action Etanercept [ee TAN er sept] is a genetically engineered fusion protein composed of two identical chains of the recombinant human TNF-receptor p75 monomer fused with the Fc domain of human IgGi. This soluble fusion protein binds two molecules of TNF, and prevents them from binding to cellular receptors. The protein does not discriminate between TNF-a and TNF- 3 (lymphotoxin). [Note Because TNF is important in modulating cellular immune responses to infection and tumors, there is some concern about the long-term use of etanercept.]... 

AMPs can act as adjuvants for adaptive immune responses, enhancing specific and protective responses. LL-37 [200], cathelin-related antimicrobial peptide (CRAMP) [189] and mouse BD-2 [201] enhanced antigen-specific humoral and cellular immune responses, and induced protective anti-tumor immunity in some conditions [200]. It has been suggested that even low doses of AMPs can influence immune responses, since LL-37 has a synergistic activity with granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-ip [155,196]. 

Benzo[a]pyrene exerts its inhibitory effects on antibody production through alterations on the normal functioning of macrophages, T cells, and B cells (Blanton et al. 1988 Zhao et al. 1990). In contrast, benzo[a]pyrene has no effect on most cellular immune responses before the appearance of tumors (Dean et al. 1983b), although benzo[a]pyrene exposure does inhibit IL-2-dependent proliferation (Myers et al. 1988). 

Investigational Therapies. As discussed above, the idiotype present on the patient s tumor cells serves as a potential target for immunotherapy. This idiotype can be used to manufacture a patient-specific vaccine. Vaccines would potentially produce both humoral and cellular immune responses, and would also be longer acting than passive immunotherapy. Several vaccines are being evaluated in clinical trials. ... 

Kunze E, Schulz H, Gabius HJ. Inability of galactoside-specific mistletoe lectin to inhibit N-methyl-N-nitrosurea-induced tumor development in the urinary bladder of rats and to mediate a local cellular immune response after long-term administration. J Cancer Res Clin Oncol 1998 124(2) 73-87. 

Some studies have attempted direct injection of DNA into tumors, either alone or in complex with lipids. Introducing DNA or RNA directly into the tumor limits immune responses sometimes elicited when viral preparations are administered. However, the efficiency of lipid-DNA to enter cells in a tumor remains a problem, as does the relatively nonspecific cellular uptake of lipid-DNA complexes. Attempts to incorporate molecules in the lipid bilayer that bind to cell surface receptor to improve cell specificity have been investigated, but the differential effects seen in vitro are not generally duplicated in vivo. Along the same line and more recently, nanoparticles has also been considered as vector for delivering therapeutic genes. An added benefit with nanoparticles is that they can also be imaged (Nie et al. 2007). 

Swainsonine may also prove to be an effective chemotherapeutic agent against certain types of cancers. Thus, swainsonine has been found to reduce tumor cell metastasis, enhance cellular immune responses and resuce solid tumor growth in... 

Guranathan S, Irvine KR, Wu CY, Cohen JI, Thomas E, Prussin C, et al. CD40 ligand/trimer DNA enhances both humoral and cellular immune responses and induces protective immunity to infectious and tumor challenge. J Immimol 1998 161(9) 4563-4571. 

TNF. Tumor necrosis factor. TNFs are among the important cytokines playing a key role in activation and induction of some immune system cells and cellular immunity processes responsible for proinflammatory and inflammatory response reactions as well. 

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