CAR-T cells (Chimeric Antigen Receptor- T cells) are T cells that have been genetically engineered to produce an artificial T cell receptor for use in immunotherapy. Chimeric antigen receptors are receptor proteins that have been engineered to give T cells the new ability to target a specific protein. This therapy use to treat several type of cancer but significantly treat leukemia. And this therapy is very effective than other.

1. Seminar topic
On
Target of CAR-T Cell Therapy
and it’s role in Immunotherapy
Presented by:- Mhd Shabbu Khan
Reg. no.- 21mpharm06
M.Pharm Pharmaceutical chemistry
Supervised by:- Dr. Vikram Deep Monga Sir
Department of pharmaceutical sciences and natural
products
Central University of Punjab Bathinda

2. Content
• Introduction of CAR-T Cell Therapy
• History of CAR-T Cell Therapy
• General information about CAR-T Cell Therapy
• Where CAR-T Cell Therapy Available
• CAR-T Cell Therapy
• Process of CAR-T Cell Therapy
• Structure and generation of CAR-T Cell Therapy
• Target of CAR-T Cell Therapy
• CAR-T Cell Therapy Clinical Trial and Side Effects
• Benefits of CAR-T Cell Therapy
• Disadvantage of CAR-T Cell Therapy
• Reference

3. INTRODUCTION Of CAR-T Cell Therapy
• Chimeric antigen receptors (CAR) are genetically encoded artificial
fusion molecules that can reprogram the specificity of peripheral
blood polyclonal T-cells against a selected cell surface target.
• CARs are genetically engineered receptors that combine the specific
binding domains from a tumor targeting antibody with T cell signaling
domains to allow specifically targeted antibody redirected T cell
activation.

4. History of CAR-T Cell Therapy
• In 1987, an Israeli immunologist, Zelig Eshhar, PhD, from The
Weizmann Institute of Science, created the first “chimeric
antigen receptor,” an engineered receptor that does not exist in
nature.
• The DNA encoding the receptor was implanted in the T cells so
they could fight and kill cancer.
• In the year 2010 the first successful cancer treatment with CAR-
T was for an advanced follicular lymphoma patient and was
reported by the lab of Steven Rosenberg, M.D., Ph.D., chief of
the SurgeryBranch in NCI’s Center for , Cancer Research.
• On August 30, 2017, tisagenlecleucel (Kymriah) was the first
CAR T-cell immunotherapy approved by the FDA. It was
approved for children and young adults aged 25 and under who
relapsed or were not responding to therapy for acute
lymphoblastic leukemia (ALL).

5. General information about CAR-T Cell Therapy
• CAR T cell therapy is a type of immunotherapy used to fight cancer
with altered immune cells.
• Success rate:- The CAR T-cell therapy success rate is about 30% to
40% for lasting remission, with no additional treatment, according
to Michael Bishop, MD, director of Uchicago Medicine’s cellular
therapy program.
• Infusion time:-The infusion of CAR –T cells typically takes 30 to 90
minutes.
• Therapy cost:- Drug acquisition is the largest component of the
cost of CAR T-cell therapy, with list prices ranging from $373,000 to
$475,000 depending on the specific drug and indication.

6. General information about CAR-T Cell Therapy
• CAR-T clinical trials have shown huge remission rates, of up to 93%, in
severe forms of blood cancer.
• CAR T-cell therapy patients stay in the hospital for at least seven days
after receiving treatment.
• T-cell transfer therapy is a type of immunotherapy that makes your
own immune cells better able to attack cancer.

7. Where CAR-T Cell Therapy Available
• Country:- China , Europe, Canada, Australia, UK, England And Scotland
or may be found in other country.
• In india:- The 4th June, 2021 was a historic day for TMH, IIT Bombay
team and cancer care in India as the first CAR-T cell therapy (a type of
gene therapy) was done at the Bone Marrow Transplant unit at ACTREC,
Tata Memorial Center in Mumbai.

8. CAR-T Cell Therapy
•T- Cells:- T cells are immune system cells that play several key roles in
the body’s fight against the disease. They help the immune system respond
to a disease and directly kill diseased cells.
•CARs:- Chimeric antigen receptors (CARs)are engineered receptors
which graft an arbitrary specificity onto T cell, these receptors are used to
graft the specificity of a monoclonal antibody onto a T cell, with transfer of
their coding sequence facilitated by retroviral vectors.
• The receptors are called chimeric because they are composed of parts
from different sources.

9. CAR-T Cell Therapy
•CAR-T Cell Therapy:-CAR T-cell therapy is a type of
immunotherapy that changes a patient’s own T cells so they are able to
recognize and attack cancer.
• T cells are taken from a patient’s blood. Then the gene for a special
receptor that binds to a certain protein on the patient’s cancer cells is
added in the laboratory.

10. Cancer can be treated with CAR-T

11. Cancer can be treated with CAR-T
FDA Approved:-
• Yescarta (Axicabtagene ciloleucel) has been approved for patients with large
B-cell lymphoma that has relapsed or does not respond to standard
treatments.
• Kymriah (Tisagenlecleucel) is for pediatric and young adult patients age 25 or
younger with B-cell acute lymphoblastic leukemia.
• To be eligible for either treatment, patients must have been treated
unsuccessfully with at least two other cancer therapies.

12. Cancer can be treated with CAR-T
Obstacle In:- Efforts to identify
unique antigens on the surface of
solid tumors have largely been
unsuccessful.
• EGFR, EGFRvIII, IL13Rα2,
HER2…
• Solid Tumor:-Components of
the microenvironment that
surrounds them conspire to
blunt the immune response.
• ECM, HSPGs, HPSE

13. The process of CAR-T Cell Therapy

14. Structure and Generation of CAR-T Cell

15. Structure and Generation of CAR-T Cell

16. Target of CAR-T Cell Therapy

17. Target of CAR-T Cell Therapy

18. Target of CAR-T Cell Therapy

19. Structure of target- CD19

20. Structure of target- CD20

21. Structure of target- BCMA

22. Structure of target-HER2

23. CAR-T Cell Therapy Clinical Trial and Side Effects
• As of August 2017, there were
around 200 clinical trials
happening globally involving CAR
T-Cells. Of those trials, around
65% were trials in which
haematological malignancies
were explored, and 80% of them
involved CD19 CAR T-Cells
targeting the B-cell cancers.
Studies had begun by 2016 to
explore the viability of other
antigens such as CD20.

24. CAR-T Cell Therapy Clinical Trial and Side
Effects
Cytokine-Release Syndrome (CRS)
• In the case of CRS, there is a
rapid and massive release of
cytokines into the bloodstream,
which can lead to dangerously
high fevers and precipitous
drops in blood pressure. CRS
symptoms can range from mild
flulike symptoms that include
nausea, fatigue, headache, chills
and fever to more serious
symptoms.
low blood pressure, tachycardia, capillary leakage,
cardiac arrest, cardiac arrhythmias, cardiac failure,
hemophagocytic lymphohistiocytosis …

25. CAR-T Cell Therapy Clinical Trial and Side Effects
• Language impairment (aphasia), confusion, delirium, involuntary
muscle twitching, hallucinations, unresponsiveness or seizures

26. CAR-T Cell Therapy Clinical Trial and Side Effects
CART-cell therapy targeting antigens found on the surface of B cells not only
destroys cancerous B cells but also normal B cells.These normal B cells are
also often killed by the infused CART cells.

27. CAR-T Cell Therapy Clinical Trial and Side Effects
A group of metabolic complications that can occur due to the breakdown of
dying cells - usually at the onset of toxic cancer treatments.

28. CAR-T Cell Therapy Clinical Trial and Side Effects
Symptoms associated with anaphylaxis include hives, facial
swelling, low blood pressure and respiratory distress.

29. Benefits Of CAR-T Cell Therapy
• HLA-independent antigen
recognition.
• Active in both CD4+ and CD8+ T-
cells.
• Target antigens include proteins,
carbohydrates, and glycolipids.
• Rapid generation of tumor specific
T-cells.
• Minimal risk of autoimmunity or
GVHD(Graft-versus-host disease).
• A living drug, single infusion.

30. Disadvantages oF CAR-T Cell Therapy
• 1) Cytokine Release syndrome CRS
(symptoms like high fever, nausea,
capillary leaky syndrome) .
• Anti IL-6 overcome the CRS toxicity.
1) Neurotoxicity( i.e. confusion,
seizures, or severe headaches.)
2) 2) Cost USD $ 475,000 by
Novartis’s which is equal to Rs
30,400,000

31. Reference
1. Jackson J, Rafiq S, Brentjens RJ. Driving CAR T-cells forward. Nat Rev Clin
Oncol. 2016;13(6):370-383.
2. Lee DW, Gardner R, Porter DL, et al. Current concepts in the diagnosis
and management of cytokine release syndrome. Blood. 2014;124(2):188-
95.
3. JacksonBarrett DM. Current status of chimeric antigen receptor therapy
for hematological malignancies. Br J Haematol. 2016;172(1):11-22.
4. Maude SL, Teachey DT, Porter DL, Grupp SA. CD19-targeted chimeric
antigen receptor T-cell therapy for acute lymphoblastic leukemia. Blood.
2015;125(26):4017-4023.
5. Maus MV, Levine BL. Chimeric antigen receptor T-cell therapy for the
community oncologist. Oncologist. 2016;21(5):608-617.

32. Thank You!