A new technological breakthrough presented at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting promises to greatly speed up the process of developing therapies to effectively treat cancer and to eliminate the terrible side effects often associated with cancer treatment. The cancer research foundation, Cancer Antibodies Inc. presented the results of a research study of their new platform which facilitates rapidly finding: sites on the surface of cancer cells that are not possessed by normal cells. multiple cancer-specific sites simultaneously. This vastly improves the probability that, if the cancer mutates and acquires resistance to a drug associated with the mutated site, that another drug that binds to a different site can be used. therapeutic agents (ex. antibodies) that target those sites. The method is based on the fact that if you introduce a human cell into a non-human vertebrate, the animal’s immune system will recognize the human cells as foreign and make antibodies against them. If antibodies are found that bind only to cancer cells, they can be used to create targeted therapies. All cells, including cancer cells, have areas on the cell surface called antigens. An epitope is the part of the antigen to which antibodies bind. Cancer Antibodies Inc. developed a novel process for filtering out the antibodies that cross react with normal cells. The resulting antibodies bind only to cancer cells and allow for the discovery of new cancer-specific surface targets (antigens). The finding of these new targets and their corresponding antibodies unlock the reality of precisely targeted treatments that do not harm normal cells. Many current therapies that involve antibodies utilize monoclonal antibodies meaning that they bind only to one specific target that has already been identified. This new approach uses polyclonal antibodies, meaning there are many different antibodies that bind to a variety of targets. The polyclonal antibodies are being used both to find new targets (sites) that were not previously known and as a delivery mechanism to preferentially kill the cancer cells. The primary reasons finding a cure for cancer has proved so difficult are that traditional cancer treatment strategies also affect normal cells. This often leads to debilitating side effects. Also, as the cancer grows and spreads, the tumor cell DNA mutates further making molecular targeted therapies ineffective. This new method offers a solution to both of these challenges: unique cancer-specific antigens are targeted and therefore normal cells are not affected. In addition, if the cancer cells mutate, the technique can be utilized to find new targets on the recently mutated cancer cells. Once unique targets on cancer cells are found, there are various ways of killing them. The scientists from Cancer Antibodies Inc. took the cancer specific antibodies that were generated and attached a toxic drug, creating something called an antibody drug conjugate (ADC). The ADC only expresses its toxicity when it is attached to a cell and the antibodies only bind to cancer cells. The cancer-specific ADCs were tested on breast cancer and normal breast cells. The cancer and normal cells were taken from the same individual and the same tissue type. The results demonstrated that the cancer cells were killed while the normal cells remained unscathed. As part of the study, it was also discovered that the antibodies derived from one person’s breast cancer killed breast cancer cells derived from another person, indicating that the targets that were found were common across more than just that individual's breast cancer. Other cancer-specific ADCs were tested on melanoma cancer cells and normal skin cells derived from the same person. The results showed that the melanoma cells were killed while the normal skin cells remained unscathed. Remarkably, the antibodies derived against melanoma were also able to kill three different strains of prostate cancer. The results of all these tests imply that: an individual’s cancer cells can contain unique cancer-specific surface antigens cancer cells that are of a similar type but from different individuals can share the same cancer-specific antigens (ex. breast cancer from different women). different types of cancer cells can have the same antigens (ex. melanoma and prostate cancer derived from different individuals). Cancer Antibodies Inc.’s unique ability to find cancer-specific antigens, and create antibodies and ADCs that target these sites has huge implications for the development of effective therapies that are tailored for each individual’s cancer as well as agents that work across individuals that have the same type of cancer and even individuals that have different types of cancer. The American Society of Clinical Oncology (ASCO) published an abstract embodying the novel method and research results in their . DOI: http://doi.org/10.1200/JCO.2022.40.16_suppl.2530. The results of the study were presented at the ASCO Annual Meeting in June 2022. Journal of Clinical Oncology More information on the process, including a video of their poster presentation at ASCO, can be viewed at: https://www.cancerantibodies.com/info/ Cancer Antibodies Inc. is seeking funding to take their discoveries out of the laboratory and apply them in the clinic.

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