QuestionQuestion

PART A.
The company recognises that Immtumomab may have potential for the treatment of colon cancer, for which treatment options are limited. Describe:
Pre-clinical work you would undertake to get Immtumomab to the point of a first in human safety trial:
i. Discuss any alterations you would want to make to Immtumomab’s structure and why
ii. Describe an in vivo mouse model that would give you information about the biodistribution of Immtumomab, include justification for your choice of mouse.
iii. Describe 3 mechanisms that your antibody might use to kill tumour cells in patients.

PART B.
The company performs a first in human clinical trial with their antibody. The antibody is safe and well tolerated, so the antibody progresses to an efficacy trial. However, unfortunately, no patients see any clinical benefit. Your company is disappointed that the antibody has not shown therapeutic benefit. However, they believe this antibody has potential, and so want to move forward with a new therapeutic approach.
Suggest an alternative therapeutic approach, using the exact same antibody, or a part of that antibody. Include discussion of:
i. The mechanism of action of your approach, and how your approach overcomes immune-evasion mechanisms exerted by the cancer cell.
ii. Any risks and/or challenges associated with your approach.
iii. Suggest preclinical in vitro and in vivo experiments you would perform to test whether your approach might be successful in the clinic.

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Discuss any alterations you would want to make to Immtumomab’s structure and why?
Immunoglobulin G (IgG) antibody is mostly used in immunocytochemistry. Structurally antibody consists of two light chains and two heavy chains. On the light chain, there are variable regions (Fab portion) that are crucial for the interaction of the antibody with antigens. The constant region (Fc portion) only binds to the particular site. In the current scenario, Immtumomab only recognizes the IMM2 on patient biopsy section, but not on control health gut tissues. Therefore, the structure of Immtumomab is colocalized, and an additional label is added to the first primary antibody to facilitate binding of an IMM2 antigen with the antibody on control health gut tissues. If the labeled protein...

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