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Vitoria Olyntho Cheryl (Jiayi) Xing Erica Zeng

Abstract

Introduction: Monoclonal antibodies (mAbs) have emerged as a promising immune-oncological approach to target cancer cells. mAbs have been seen to outperform traditional drug treatments in treating severe cancers despite their low relative cytotoxicity due to their high selectivity. CD22 is expressed in 60-90% of individuals with B-cell Acute Lymphoblastic Leukemia (B-ALL), and is rapidly internalized when bound to an antibody, making it an effective point of entry for cytotoxic agents. Epratuzumab is an anti-CD22 mAb, effective against B-ALL. Epratuzumab-SN-38 (Emab-SN-38) and Inotuzumab ozogamicin (InO) are promising anti-CD22 Antibody-Drug Conjugates (ADCs).


Methods: Epratuzumab, Inotuzumab, and Emab-SN38 treatments will be evaluated in vitro and in vivo. B lymphocytes collected from a 30-35-year-old R/R ALL patient will be purified and expanded. A cell culture assay will evaluate the treatments. Cells will be engrafted into humanized mice. Mice will be assorted into four treatment groups: saline (control), Epratuzumab, Inotuzumab, and Emab-SN-38.  Quantitative flow cytometric analysis will be used to assess treatment effectiveness. Complete Response will be determined as ≅ zero human leukemic cells, Partial Response as ≤5% cells, and Remission as >5% cells or with identifiable clinical signs. Mice will be followed for 6 months after the last dose of treatment to assess for relapse and survival rate.


Results: It is expected that all three treatments will result in more significant results regarding tumour shrinkage and rate of cancer growth than saline. The ADCs are expected to perform better than unconjugated Epratuzumab. Relapse and Adverse Event rates are expected to be lowest in Epratuzumab-SN-38.


Discussion: The comparison of the effectiveness of these treatments are expected to establish Emab-SN-38 as a potential treatment option and propel research into other cytotoxic agents which could be used in conjugation with Epratuzumab and other mAbs. 


Conclusion: ADCs combine the cytotoxicity of chemotherapy and the specificity of mAbs to treat R/R ALL. The ADCs are expected to outperform Epratuzumab in decreasing leukemic cell load given their potent targeted cytotoxicity. Emab-SN-38 is expected to be less toxic but as effective as Inotuzumab. These results could inform research on safer and more potent ADCs in treating R/R ALL via CD22.

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Section
Research Protocol