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IMMUNOTHERAPHY FOR HIV INFECTION
Transcript of IMMUNOTHERAPHY FOR HIV INFECTION
The effectiveness of oral antiretroviral treatment
Given the effectiveness of oral antiretroviral treatment, what advantage might be proffered by inoculation with monoclonal antibodies? The answer may be a long-term effect and an alternative treatment for those in whom antiretroviral treatment has failed. Moreover, a combination of conventional drugs and immunotherapy may be better than either alone. One of the problems with antibody therapy is the need for repeated injections of the monoclonal antibody in order to maintain levels sufficient to control the virus.
The danger of an activated immune system
Progressive HIV infection is characterized by persistently increased levels of various soluble inflammatory markers, dysregulation of T cell surface markers, and upregulation of receptors for immune suppressor signals such as PD-1 and cytolytic T-lymphocyte antigen (CTLA)-4. This inappropriate immune activation is partly due to a persistent VL, but in addition endotoxins originating from microbial translocation through a “leaky gut” and “hypersensitivity” to type 1 IFN have been implicated (for review see .
Immunotherapy is the "treatment of disease by inducing, enhancing, or suppressing an immune response". Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies, while immunotherapies that reduce or suppress are classified as suppression immunotherapies.
The exact mechanism through which monoclonal antibodies work remains to be elucidated. Their effectiveness as potent neutralizers of infectious HIV particles has been established, but it is also thought that they may reduce the number of virus-producing cells. Such destruction of the factories of virus production may be mediated through antibody-dependent cellular cytotoxicity or through cell lysis by complement. The number of cells infected with viral DNA in lymph nodes and mucosa also diminished, according to analysis of biopsy specimens; one antibody in particular was effective in reducing viral load and the number of infected cells.
Potent neutralization of anti-HIV
Potent neutralization of anti-HIV monoclonal antibodies can also prevent new infection when locally administered before a mucosal SHIV challenge.
It is often assumed that mucosal immunity requires secretory IgA responses, although we know that protection against cervical cancer through human papillomavirus vaccines is mainly achieved through IgG. Watkins et al.5 recently reported that the use of passive monoclonal antibody protection with dimeric IgA1 (which captures virus particles and prevents their transcytosis across mucosal cells) was more effective than direct neutralization of SHIV, whereas the nontranscytotic dimeric IgA2 isotype of the same monoclonal antibody offered poor protection.
Monoclonal antibodies already have a well-established role in immunotherapy for cancer and autoimmune disease. There is no reason to hesitate to explore their clinical potential for use in the control of chronic infection with viruses such as HIV-1, especially given the recent data on the effects of treatment with highly potent, broadly neutralizing monoclonal antibodies.
Dendritic cell-based immunotherapy
T-cell adoptive transfer
Autologous immune enhancement therapy
Genetically engineered T cells
The obvious goal of therapeutic vaccination is to stimulate effective HIV-specific T cell responses, primarily cytolytic/virus suppressive CD8 T cells with supporting CD4 T cell help, while avoiding increased HIV-susceptibility of target cells. To that end, protein or particulate antigen is conceptually not the best option, since it primarily results in CD4 T and B cell activation: antibodies are considered ineffective and CD8 T cells seem essential in immune protection post infection.