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Antibody Therapy
Although chemotherapy is the most commonly used treatment when it comes to acute lymphoblastic leukemia, it is not always the most effective. The drugs given to the patient are not very selective, so while they are generally effective at killing diseased cells, they also kill off healthy cells. Another issue is that chemotherapy does not always work for everyone, so many patients may relapse after their treatment.

Antibody therapy is another type of treatment that has had some success in treating ALL. In this treatment, toxic agents are bound to antibodies that will target specific antigens on cells. These antigens are expressed on the outside of the cells, and make for easy targets for drug delivery. Once the antibody binds to the antigen, the antigen-antibody complex is taken into the cell, where the toxic agent can then destroy the infected cell

When researchers looked at ALL tumor cells, they found that antigens such as CD20 and CD22 are expressed more in diseased cells than healthy cells, making them ideal targets for antibody treatment. Unfortunately, since antibody therapy is a relatively new treatment, drugs that could be used for treatment have not yet been completely studied, and therefore are not fully available as an option. However, early results show promise in the future success of these drugs.

Rituximab
One of the drugs currently being evaluated for the treatment of ALL is called Rituximab. Rituximab targets the CD20 antigen attached to B-cells, and was approved for the treatment of non-Hodgkin lymphoma in 1997. It has been used to treat patients with Burkitt’s lymphoma with some positive results, and therefore is a viable candidate for treatment of ALL. When Rituximab was incubated with cancerous cells, it was found to induce cell death. When tested in people with ALL, the 3-year survival rate of continuous remission improved compared to those treated with just chemotherapy. When Rituximab was added to chemotherapy treatment, it improved the percent of patients that achieved minimal residual disease (MRD) negative status, meaning that there were little to no cancer cells found in the body after treatment. This is a positive sign for future treatments and developments of CD20-targeting drugs.

Epratuzumab-SN-38
Unlike Rituximab, Epratuzumab-SN-38 (Emab-SN-38) targets the CD22 antigen, which is more commonly expressed on diseased B-cells, making it a better target for antibody therapy. Unfortunately, this treatment has not yet completed enough clinical trials to be available for the general public, although there are many studies that are going on today. When incubated with diseased cells, Emab-SN-38 successfully caused complete cell death. When used with normal chemotherapy treatments, Emab-SN-38 was not found to improve the overall percent of patients achieving a second complete remission. However, twice as many patients treated with Emab- SN-38 could be declared as minimal residual disease negative, as opposed to those who were treated with chemotherapy alone. Although Emab-SN-38 does not help to improve the amount of people who achieve remission, it does significantly increase the amount of people who are MRD negative, which is a good sign for future developments.

HB22.7-SAP
HB.22.7-SAP is a CD22-targeting antibody that is conjugated to a protein toxic agent called saporin. This molecule has only been tested in cell cultures and mice so far, but it has shown promising results. In the cell tests, it was seen that very little HB22.7-SAP is needed to cause cell death, which is an ideal result ]. When mice were injected with the drug, they remained alive more than twice as long as the control group, which was not given the drug. It was also seen that the treated mice had normal amounts of white blood cells in their bodies at the end of the study, while the control group had decreased amounts of these cells; decreased amounts of white blood cells is indicative of leukemia. This molecule shows promise as a potential drug candidate for the treatment of ALL due to its effectiveness at killing infected cells in mice, although it would need much more development before it could be used in human patients.

CMC-544: Inotuzumab Ozogamicin
CMC-544, also known as inotuzumab ozogamicin (IO), is another CD22-targeting drug candidate that has calicheamicin (CMC) attached to it. CMC is a highly toxic agent that causes the DNA inside a cell to split in half and die, making it an ideal molecule to attach to a CD22 antibody. Inotuzumab ozogamicin is a recently discovered drug, and so many tests still need to do done to determine if it is a suitable candidate for antibody therapy in people. However, in preclinical tests in cell cultures, IO inhibited cancer cell growth as well as induced cell death that increased as the amount of the CD22 antigen available increased. With more research being devoted to studying IO, there is a high possibility that this drug may become a viable candidate for treatment of ALL.

Bs20X22
Bs20x22 is an antibody conjugate that was originally developed for the treatment of Non-Hodgkin Lymphoma (NHL). Since ALL is a type of NHL, this drug could also be used to treat patients with ALL. Bs20x22 is different from most other antigen-targeting drugs because while most of those target only one antigen, Bs20x22 targets both the CD20 and CD22 antigens expressed on B-cells. This gives the drug more potential targets to bind to, since it can bind to both CD20 and CD22 antigens. Since both of these antigens are expressed on B-ALL cells, this makes for an ideal drug candidate. The structure for this drug is based off of two parent drugs, Rituximab and HB22.7, and binds to the antigens just as well as its parent molecules. When the drug was tested in various NHL cell cultures, it was found to be more toxic than the parent drugs as well. This drug could be a starting point for many other molecules that could de developed to target more than one antigen.