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Monoclonal antibody therapy for cancer

Infection and responseMonoclonal antibodies (biology only) (HT only)

Flashcards

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What role do hybridoma cells play in monoclonal antibody production?

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Hybridoma cells produce identical monoclonal antibodies indefinitely after fusion of antibody-producing spleen cells with myeloma cells .

Key concepts

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Definition and therapeutic purpose

Monoclonal antibodies are identical antibody molecules produced from a single clone of cells that bind a single, specific antigen. Therapeutic use involves exploiting this specificity to direct treatment to particular cell types that express the antigen. The primary purpose of targeted delivery is to increase damage to diseased cells while reducing side effects on healthy cells .

Mechanism of targeting and delivery

Antibodies bind to a unique antigen on the surface of the target cell. Conjugation links a toxic drug or a radioactive isotope to the antibody so that the payload is carried and retained at the antigen-bearing cell. Binding causes the payload to concentrate at the tumour or infected tissue, producing localised cell death either directly (toxin) or via ionising radiation (isotope) .

Antibody-drug conjugates and radioimmunotherapy

Antibody-drug conjugates (ADCs) attach a cytotoxic drug to the antibody using a chemical linker that remains stable in the bloodstream but releases the drug at the target. Radioimmunotherapy attaches a radioactive atom; emitted radiation kills nearby cells by damaging DNA. Both methods rely on antibody specificity to concentrate lethal agents at diseased cells and reduce systemic exposure compared with non-targeted treatments .

Clinical example and mode of action

Some monoclonal antibodies act by blocking growth signals on cancer cells, slowing tumour growth. Other therapeutic antibodies act as delivery vehicles for toxins or isotopes. Herceptin exemplifies a targeted antibody that blocks growth-factor receptors on certain breast cancer cells, reducing cell division; similar antibodies can be adapted to carry cytotoxic payloads to cells with matching antigens .

Limitations, side effects and safety factors

Therapeutic success depends on antigen specificity, antigen expression only on diseased cells, and effective delivery of the payload. Off-target binding causes damage to healthy tissue. Immune reactions against therapeutic antibodies reduce efficacy or cause adverse effects. Tumour heterogeneity and antigen loss cause reduced targeting and treatment resistance. Radiation safety and controlled release of cytotoxins present additional clinical challenges .

Key notes

Important points to keep in mind

Therapeutic monoclonal antibodies rely on the antigen being mostly unique to diseased cells.

Antibody specificity determines how well the payload concentrates at the target.

Stable linkers in ADCs prevent premature systemic release of toxins.

Radioimmunotherapy kills nearby cells through emitted radiation even without internalisation.

Immunogenicity and tumour heterogeneity reduce long-term effectiveness.

Poor tumour penetration limits delivery to all cancer cells; dosage adjustments cannot fully overcome this.

Off-target antigen expression is the main safety limitation for targeted delivery.

Combination therapies reduce the chance of antigen-loss escape by tumours.

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