It's basically just a rash at the injection site. Sometimes it's more serious, but this is more serious with mouse antibodies
Bavi is a chemeric Mab so most of the HAMA issues were resolved. We have not seen many in any of the trials. I.E....Results: Twenty-six patients were accrued. No maximum tolerated dose was reached. Six serious adverse events occurred in five patients, including one pulmonary embolism at 3 mg/kg, which was the only dose-limiting toxicity (DLT) in the study. Conclusions: Bavituximab was well tolerated at doses ranging up to 3 mg/kg weekly. Pharmacokinetic studies support a weekly dosing regimen. Additional phase I and II clinical trials are in progress to investigate bavituximab in combination with chemotherapy and other molecularly targeted agents.
Problems with monoclonal therapy Mouse antibodies are "seen" by the human immune system as foreign, and the human patient mounts an immune response against them, producing HAMA ("human anti-mouse antibodies"). These not only cause the therapeutic antibodies to be quickly eliminated from the host, but also form immune complexes that cause damage to the kidneys. Link to discussion of immune complex disorders.
(Monoclonal antibodies raised in humans would lessen the problem, but few people would want to be immunized in an attempt to make them, and most of the attempts that have been made have been unsuccessful.)
However, using genetic engineering it is possible to make mouse-human hybrid antibodies to reduce the problem of HAMA.
Chimeric antibodies. The antibody combines the antigen-binding parts (variable regions) of the mouse antibody with the effector parts (constant regions) of a human antibody. Infliximab, rituximab, and abciximab are examples. Humanized antibodies. The antibody combines only the amino acids responsible for making the antigen binding site (the hypervariable regions) of a mouse (or rat) antibody with the rest of a human antibody molecule thus replacing its own hypervariable regions. Daclizumab, Vitaxin, Mylotarg®, Herceptin®, and Xolair® are examples.
In both cases, the new gene is expressed in mammalian cells grown in tissue culture (E. coli cannot add the sugars that are a necessary part of these glycoproteins). Looking ahead
Other ways of solving the problem of HAMA are being vigorously pursued. Transgenic mice. One of these is to exploit transgenic technology to make transgenic mice that:
have had human antibody gene loci inserted into their bodies (using the embryonic stem cell method). Link to discussion of the organization of human antibody genes. Link to discussion of how transgenes are introduced into embryonic stem cells. have had their own genes for making antibodies "knocked out". Link to discussion of how this is done.
The result is a mouse that
can be immunized with the desired antigen produces human, not mouse, antibodies against the antigen can yield cells to be fused with myeloma cells to manufacture all-human monoclonal antibodies.
Phage display is another technique for making all-human monoclonal antibodies. Link to discussion. Monoclonal T-cell Receptors (TCRs)
Antibodies can bind to molecules expressed at the surface of target cells (as well as to soluble molecules) but are not effective against the peptide fragments that antigen-presenting cells contain tucked within their histocompatibility molecules. T-cell receptors are the ligands needed for that job. [Discussion]
So monoclonal antibodies are not effective against intracellular antigens, e.g. virus-encoded proteins and tumor-specific antigens. But now progress is being made toward the development of monoclonal T-cell receptors (aß TCRs). Two ways in which these molecules could be helpful:
Transforming normal T cells — whatever their natural specificity — so they also express a new TCR of desired specificity (and high affinity). These could then be introduced into a cancer patient to target the tumor-specific antigens [An example] or into an AIDS patient to target HIV-infected cells. Preparing a fusion protein of the engineered TCR conjugated to an effector molecule to destroy cells expressing the target MHC-peptide complex.
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