Anticancer Drugs, Cancer Vaccine and Immunotherapy PDF

Anticancer Drugs Cancer Vaccine and Immunotherapy Leow Chiuan Yee, PhD School of Pharmaceutical Sciences Universiti Sains Malaysia  Lecture outline We l e a d History of cancer immunotherapy Cancer immunotherapy Immune checkpoint inhibitor...

Anticancer Drugs Cancer Vaccine and Immunotherapy Leow Chiuan Yee, PhD School of Pharmaceutical Sciences Universiti Sains Malaysia  Lecture outline We l e a d History of cancer immunotherapy Cancer immunotherapy Immune checkpoint inhibitors Monoclonal antibody therapy Cancer vaccines Adoptive T-cell transfer therapy History of immunotherapy We l e a d 3 Kirkwood, J. M., at. al., J. Clin. Oncology (2008) History of immunotherapy We l e a d 4 Kirkwood, J. M., at. al., J. Clin. Oncology (2008) History of immunotherapy We l e a d 5 Kirkwood, J. M., at. al., J. Clin. Oncology (2008)  James Allison and Tasuku Honjo found ways to remove the “brakes” that prevent the immune system from attacking tumor cells. Discoveries about ways to harness the immune system to attack cancer have won the Nobel Prize in Physiology or Medicine 2018. 6 T cell activation signaling We l e a d Gutcher I & Becher B (2007). J Clin Invest. 7 T-cell exhaustion signaling We l e a d Cancer Cancer 8  Cancer immunotherapy We l e a d Immunotherapy demonstrates remarkable potential to treat cancers. It harnesses the body's immune system to target and destroy cancer cells. Immunotherapy offers the promise of durable responses and potential cures for some cancer patients including advanced stage of cancers. 9 Zhang, Z., et. al., Front. Immunol. (2021)  Cancer immunotherapy We l e a d Goals: ↑ Antitumor response ↓ Immunosuppresssion ↑ Immunogenicity of tumors Cancer immunotherapy approaches We l e a d 11 Gupta, R., et. al., Trends in Cancer (2022) Cancer cell therapy landscape by year and type We l e a d 12 Saez-Ibañez, A. R., Nature Reviews Drug Discovery (2022) Traditional and modern strategies used in cancer therapy  Traditional and modern strategies used in cancer therapy Aspect Traditional Cancer Therapy Cancer Immunotherapy Enhances body's immune system to fight Mechanism Directly targets and kills cancer cells cancer Monoclonal antibodies, immune checkpoint Methods Surgery, chemotherapy, radiotherapy inhibitors, CAR-T cells High specificity, targets cancer cells more Specificity Often non-specific, affecting healthy cells too precisely Side Effects High, including hair loss, fatigue, nausea Generally lower, immune-related side effects May require continuous treatment, resistance Potential for long-lasting remission, durable Long-Term Efficacy possible responses Cost Variable, often high Often higher due to advanced technology Highly personalized, tailored to individual’s Personalization Less personalized, one-size-fits-all approach tumor Mechanism of Resistance Cancer cells can develop resistance to drugs Immune evasion strategies by cancer cells Impact on Immune System Generally suppressive Boosts and educates the immune system Availability Widely available, standard treatment Emerging, specialized centers  Types of cancer immunotherapy We l e a d Immunotherapy of cancer Immune Monoclonal Cancer Adoptive checkpoint antibodies vaccines T-cell transfer inhibitors therapy  Immune checkpoint inhibitors We l e a d  Immune cells (T cells), have receptors on their surface that allows them to be turned on or turned off. These stop signals are like brakes that keep the immune system in check and are known as checkpoints.  Many cancers hijack these brakes by making a molecule that triggers them, preventing the immune system from destroying cancer cells.  Checkpoint inhibitor drugs release the brakes so the immune system can turn on T cells to kill the cancer cells.  a) CTLA-4 blocker b) PD-1 and PD-L1 blocker Immune checkpoint inhibitors Immune checkpoint inhibitors (cont…) We l e a d  Cytotoxic T cell activator-4(CTLA-4) inhibitor- Iplimumab - Treat Melanoma of skin.  PD-1 and PD-L1 inhibitors- Pembromizumab (PD-1) - Bladder cancer, melanoma. Atezolimumab (PD-L1) - S.C. lung cancer. Immune checkpoint inhibitors in cancer therapy 19  Monoclonal antibody therapy We l e a d  Monoclonal antibodies that bind only to cancer cell-specific antigens and induce an immunological response against the target cancer cell.  Naked mAbs: antibodies that work by themselves. boost a person’s immune response against cancer cells. blocking specific proteins that help cancer cells grow. Eg. Trastuzumab-HER2  Conjugated mAbs: are those joined to a chemotherapy drug (e.g. ADC), radioactive particle, or a toxin  Antibody–drug conjugate (ADC) is typically composed of a monoclonal antibody (mAbs) covalently attached to a cytotoxic drug via a chemical linker. https://njbio.com/antibody-drug-conjugates/  Cancer vaccines We l e a d  The goal of vaccine therapy is to make the immune system attack any cancer cells.  Unlike vaccines that protect from an infection, such as the Covid-19 vaccines (prophylactic), cancer vaccines treat people who already have the disease (therapeutic).  They are designed to help the patient’s immune system recognize and then kill cancer cells – and prevent them from coming back.  Types of cancer vaccine We l e a d Tumor cell vaccines: made from actual cancer cells that have been removed during surgery. Antigen vaccines: These vaccines boost the immune system by using only one antigen rather than whole tumor cells. Dendritic cell vaccines: special antigen presenting cells (APC) for the induction of antigen specific T cell response against cancer cells. mRNA vaccines: When the vectors are then injected into the body, this mRNA might be taken up by cells and can instruct them to make specific antigens.  Dendritic cell vaccines We l e a d Example: Sipuleucel-T: Prostate cancer vaccine 1. The Antigen Presenting Cells (APCs) from a metastatic prostate cancer patient are collected and cultured in the presence of prostatic acid phosphatase (PAP) --- a cancer neoantigen, to generate a tumor specific response towards cancer cells. 2. PAP linked to Granulocyte macrophage colony stimulating factor (GM- CSF) is presented to APCs to enhance immune response and antigen presentation. 3. These stimulated APCs are then injected back into the patient to achieve an autologous cellular response to recognize and kill the cancer cells. Dendritic cell based vaccines in cancer treatment https://www.sciencedirect.com/science/article/abs/pii/S1740676506000435  Adoptive T-cell transfer therapy We l e a d  Adoptive T-cell transfer therapy uses a person’s immune cells (T cells) to fight cancer.  Researchers have found immune cells deep inside some tumours and have named them tumour-infiltrating lymphocytes (TILs). Clinical application of gene-modified T cells Park, TS. (2011)  Adoptive T-cell transfer therapy We l e a d 1. Blood sample is taken from the patient. 2. Immune cells (T cells) that recognize cancer cells are isolated. 3. T cells can also be taught to recognize cancer cells in the lab. 4. The T cells are grown into large population. 5. The T cells or modified T cells are introduced back to the patient. 6. These T cells will recognize and kill cancer cells.  Conclusion We l e a d  Cancer is a disease which is spreading globally due to changing lifestyle and environment.  Newer strategies for the treatment of cancer which should be cost-affordable and having less side effect.  Immunotherapy can be considered to be the future of cancer therapy as it activates the body’s own immunity and has less toxicity which is the main drawback of radiation and chemotherapy.  We l e a d Thank you! 31