L6 Biological cancer therapy: Med Difficult

This presentation covers various antineoplastic agents, including those related to cellular, biological, and antibody therapies.
The objectives include understanding immunotherapy principles, molecular mechanisms and targets of immunomodulatory inhibitors (immune-checkpoint inhibitors), differentiating between various immuno-therapeutic agents based on specific targets, and comparing anticancer vaccines and cellular therapies based on composition and targets.
A clinical pharmacology overview of anticancer agents in each biological class is also discussed.

The presentation details various classes of chemotherapeutic agents, including their mechanisms of action.
6-Mercaptopurine and 6-Thioguanine inhibit purine synthesis, while PALA inhibits pyrimidine biosynthesis. Hydroxyurea inhibits ribonucleotide reductase.
Methotrexate inhibits dihydrofolate reduction and purine synthesis. Camptothecins, etoposide, teniposide, and daunorubicin/doxorubicin block topoisomerase function.
Protein tyrosine kinase inhibitors (e.g., Bortezomib) block protein kinase activity.
Some additional classes target DNA synthesis, form adducts with DNA, deaminate asparagine, inhibit protein synthesis, or inhibit microtubule function.

The subject matter of this section is using the immune system in cancer treatment.
The immune system can naturally detect and destroy abnormal cells, but sometimes cancer cells evade detection by reducing tumor antigen expression or inducing immune cell inactivation by expressing surface proteins or signaling pathways in the microenvironment to promote tumor proliferation.

Immunotherapies strengthen immune responses against tumors by either stimulating specific immune system components or counteracting signals produced by cancer cells that suppress immune responses.

Checkpoint proteins regulate T-cell activity, and inhibitors can release the brakes on immune responses against cancers.
CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) and PD-1 (programmed cell death protein 1) are checkpoints that block T-cell activation. Inhibitor drugs can release the brakes on responses to cancer cells.

This section covers immuno-stimulants/immune system modulators and different types of immunotherapy.
Different types of cellular immunotherapy such as naked monoclonal antibodies, immunotoxins, and radioimmunotherapy are covered.

T-cells are capable of attacking tumor cells. Failures of immune surveillance lead to cancer development. Immunostimulants work by boosting the body's immune defenses through non-specific agents.
This section introduces examples like aldesleukin (Proleukin®) – a recombinant interleukin-2 (IL-2) product that activates cellular immunity and increases cytokine production – as well as denileukin diftitox (Ontak®), which is a combined product of IL-2 and diphtheria toxin to target cells expressing the interleukin-2 receptor.
Another immunostimulant class presented is recombinant interferon alfa, including its role in treating hairy cell leukemia, AIDS-related Kaposi's sarcoma, and chronic myelogenous leukemia (CML).

The information regarding the different categories of monoclonal antibodies, such as chimeric, reduced humanized, and humanized, is discussed.
There is also information about ADC = Antibody-Dependent Cellular Cytotoxicity and CDC = Complement Dependent Cytotoxicity.
The section also contains information about monoclonal antibody nomenclature and its general format.
Specific examples of monoclonal antibodies, including their targets and mechanisms of action (MOA) are also mentioned

This section details the use of monoclonal antibodies (mAbs) to modulate immune checkpoints.
Examples like Ipilimumab, Nivolumab, and Pembrolizumab are provided, each impacting specific checkpoint proteins (CTLA-4 and PD-1) to boost or adjust immune cell activity against tumors..mAbs are frequently used in combination.
This section also contains information about clinical trials, courses of treatment, etc.

This section presents naked monoclonal antibodies with specific examples.
The mechanisms of action (MOA) are thoroughly explained, and the target antigens for these antibodies and therapeutics are outlined. Specific examples like Rituximab, Trastuzumab, Cetuximab, and their mechanisms are described.

VEGFRs are a specific target class of receptors with binding mechanisms to VEGFs which stimulate and propagate cascades to stimulate multiple cell types involving development.

This section discusses the family of cell-surface receptors (TKRs) that bind to vascular endothelial growth factors (VEGFs) to trigger signaling cascades, which stimulate various functions.
Different types of VEGFs are mentioned and correlated to the different functions they trigger on cell types. This section also covers cross-talk between receptors and their functions on cell survival and signal cascades.

This section examines naked monoclonal antibodies, including examples like Bevacizumab, its mechanisms of action, and therapeutic applications.
The properties and specific functions of these antibodies are further expounded. Also, details on the use and dosage of these medicines is included

The primary mechanism of ADC action relies on targeted delivery of cytotoxic agents by ADCs, which are subsequently internalized within receptors and release inside the cell.

Immunotoxins are antibodies designed to deliver a toxic payload to cancer cells, such as Gemtuzumab ozogamicin. This section explains the MOA, describing that following binding to an antigen, the antibody-drug complex is internalized, and the calicheamicin portion is released, leading to DNA strand breaks. Specific clinical applications, targets, and the process of drug release within the cell are discussed
Brentuximab vedotin (Adcetris®) is also presented as part of this discussion and its MOA described.

This section details radioimmunotherapy, utilizing antibody conjugated with radioisotopes.
This targeting and method of delivery lead to a treatment process that involves inducing apoptosis via complement dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). Specific isotopes and diagnostic methods are also included, as well as uses on patients

Common side effects are summarized.
Various side effects of immunotherapy, such as swelling, allergic reactions, flu-like symptoms, digestive issues, blood pressure changes, myocarditis, kidney failure, leukopenia, and infections (e.g., tuberculosis)