This document discusses cancer vaccines and oncolytic viruses. It describes two types of cancer vaccines - prevention vaccines which protect against cancers like HPV and hepatitis B, and treatment vaccines which can prevent cancer recurrence, destroy remaining cancer cells, or stop tumor growth. Limitations of treatment vaccines include cancer's ability to suppress the immune system. It then discusses Provenge, the first FDA-approved cancer treatment vaccine for prostate cancer. Next, it summarizes MD Anderson's Moon Shots Program and their personalized colorectal cancer vaccine approach. It concludes by outlining Stanford's promising two-part cancer vaccine and the mechanism of oncolytic viruses in directly killing cancer cells and activating T cells against tumors.

1. Cancer Vaccines and
Oncolytic Viruses

2. Vaccines are medicines that help the body fight
disease. They can train the immune system to
recognize and destroy harmful substances. There are
2 types of cancer vaccines:
- Prevention vaccines
- Treatment vaccines

3. Cancer Prevention vaccines
There are 2 types of cancer prevention vaccines approved by
the U.S. Food and Drug Administration (FDA):
- HPV vaccine: protects against the human papillomavirus
(HPV) Which is associated with Cervical,Vaginal,Penile and Anal
Cancers
- Hepatitis B vaccine: prevent HCC

4. Cancer Treatment vaccines
 Used for people already diagnosed with cancer. The vaccines may:
- Prevent the cancer from coming back
- Destroy any cancer cells still in the body after other treatments have
ended
- Stop a tumor from growing or spreading.

5. Limitations of cancer treatment vaccines
 Cancer cells suppress the immune system.
 Cancer cells develop from a person’s own healthy cells. The immune
system may ignore the cells instead of finding and destroying them.
 Larger or more advanced tumors are hard to get rid of using only a
vaccine. This is one reason why doctors often give people cancer vaccines
with other treatments.
 People who are sick or older can have weak immune systems. Their
bodies may not be able to produce a strong immune response after
vaccination.

6. Most cancer treatment vaccines are only available
through clinical trials.
But in 2010, the FDA approved PROVENGE®
(Sipuleucel-T) for men with metastatic resistant
prostate cancer.

7. PROVENGE® (sipuleucel-T)
PROVENGE® is a personalized immunotherapy that
activates immune system to seek out and attack
advanced prostate cancer.
The treatment costs about 93.000 $.

8. Technique
 Immune cells (immature Antigen Presenting Cells) are extracted
from the patient by leukapheresis.

9. Antigen Presenting Cells (APCs)
 Key component of immune system. Engulf harmful agents which are processed
into fragments and presented as antigens on the surface of the APCs.
 Upon maturation, APCs activate T Cells which proliferate and attack cells that
express the original antigen.

10. Antigen Presenting Cells (APCs) sent to manufacturing facility and
exposed to recombinant antigen that functions as prostate cancer
associated antigen.
This antigen consists of two components :
- Prostatic Acid Phosphatase (PAP)
- Granulocyte Macrophage Colony Stimulating Factor
(GM-CSF)

11. Prostatic Acid Phosphatase (PAP)
A protein that is highly expressed in prostate cancer. (found in
95% of prostate cancers).

12. Granulocyte Macrophage Colony
Stimulating Factor (GM-CSF)
 Immune cell activator, supports APCs maturation.

13.  PAP-GM-CSF antigen is cultured with patient’s APCs.

14.  Patient’s APCs engulf and process the recombinant antigen, they begin to
mature and present the antigen on their surface.
 This processing occurs outside of the body to support APCs activation and
maturation by removing the cells from the immunosuppressive environment
created by the patient’s cancer cells.

15.  After 2-3 days, the fully mature APCs become PROVENGE®

16.  In patient’s body, Provenge activates the patient’s resting T Cells
and induces their proliferation.

17.  The Provenge-activated T Cells are able to recognize,
target and attack PAP antigen expressing prostate
cancer cells.

18. At Phase 3 clinical trial, Provenge showed a median OS
(Overall Survival) benefit of 4.1 months compared with the
placebo (P = 0.032).

19. MD Anderson's Moon Shots
Program

20.  Launched by The University of Texas MD Anderson Cancer Center.
 The Moon Shots Program is focused on thirteen cancer types.
 B-CELL LYMPHOMA MOON SHOT
 BREAST CANCER MOON SHOT
 COLORECTAL CANCER MOON SHOT
 GLIOBLASTOMA MOON SHOT
 HPV-RELATED CANCERS MOON SHOT
 LEUKEMIA (CLL) MOON SHOT
 LEUKEMIA (MDS AND AML) MOON SHOT
 LUNG CANCER MOON SHOT
 MELANOMA MOON SHOT
 MULTIPLE MYELOMA MOON SHOT
 OVARIAN CANCER MOON SHOT
 PANCREATIC CANCER MOON SHOT
 PROSTATE CANCER MOON SHOT

21. COLORECTAL CANCER MOON SHOT
They building a personalized vaccine for each individual
patient.
This vaccine is being used as a treatment, rather than for
prevention.

22.  Small piece of tumor is
removed
How They Identify Personalized Targets

23.  Sample is sent to the lab and divided into 3 pieces.

24.  Isolate DNA to identify
mutations present in
the tumor.

25.  Isolate RNA to find out
which of these mutations
are expressed at the
protein level.

26.  Identify the targets
directly from the
tumor.

27.  All data are integrated
together using sophisticated
bioinformatics to identify the
top 10 targets for each
patient, which then goes into
the vaccine.

28.  The vaccine is used
alongside with
Keytruda
(Pembrolizumab)
which is a PD-1
Inhibitor.

29. Stanford Cancer Vaccine

30.  On January 31 2018, a research team at Stanford University Published a
study about Cancer Vaccine that eliminates Tumors in mice.
 Method works to reactivate the cancer-specific T cells by injecting two
immune-stimulating agents directly into the tumor site.
 1st agent is a short sequence of DNA called a CpG oligonucleotide, which
activates receptor called OX40 on the surface of the T cells.
 The 2nd is an antibody that binds to OX40, activates the T cells to lead the
charge against the cancer cells.
 Because the two agents are injected directly into the tumor, only T cells that
have infiltrated it are activated. In effect, these T cells are “prescreened” by
the body to recognize only cancer-specific proteins.

31.  The approach worked startlingly well in laboratory mice with
transplanted mouse lymphoma tumors in two sites on their
bodies. Injecting one tumor site with the two agents caused the
regression not just of the treated tumor, but also of the second,
untreated tumor.

32.  87 of 90 mice were cured of the cancer. Although the cancer
recurred in three of the mice, the tumors again regressed after a
second treatment.
 This approach bypasses the need to identify tumor-specific immune Targets
and doesn’t require activation of the whole immune system or customization
of patient’s immune cells.

33. Oncolytic Viruses

34. Oncolytic Viruses
 Some viruses tend to infect and kill tumor cells. Known as oncolytic viruses.
 There are 2 main ways that oncolytic viruses help fight cancer:
 1st: they kill cancer cell directly when they infect these cells and cause them
to burst.

35.  2nd: when the
cancer cells die,
they release
antigens into the
body.

36. The immune system takes up those antigens, which alerts
and activates T Cells to attack cancer through out the
body.

37. Then T Cells attack cancer through out the body.

38.  On October 2015 T-VEC (Imlygic®) - a modified version of herpes simplex
virus (HSV) - was approved by FDA for treatment of melanoma.

39.  Imlygic® has been approved for use only in melanoma cases in
which the lesions cannot be surgically removed.
 Imlygic® is used as intralesional injection.
 Imlygic® has limited effect on tumors that are not near the skin.
 In the phase 3 trial, 64% of the injected tumors on and just below
the skin shrank to at least half of their original size.

40. Thank You