Cancer Vaccines and Oncolytic Viruses

Cancer Vaccines and Oncolytic Viruses

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  Cancer Vaccines and OncolyticViruses
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  Vaccines are medicinesthat 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
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  Cancer Prevention vaccines Thereare 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
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  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.
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  Limitations of cancertreatment 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.
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  Most cancer treatmentvaccines are only available through clinical trials. But in 2010, the FDA approved PROVENGE® (Sipuleucel-T) for men with metastatic resistant prostate cancer.
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  PROVENGE® (sipuleucel-T) PROVENGE® isa personalized immunotherapy that activates immune system to seek out and attack advanced prostate cancer. The treatment costs about 93.000 $.
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  Technique  Immune cells(immature Antigen Presenting Cells) are extracted from the patient by leukapheresis.
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  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.
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  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)
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  Prostatic Acid Phosphatase(PAP) A protein that is highly expressed in prostate cancer. (found in 95% of prostate cancers).
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  Granulocyte Macrophage Colony StimulatingFactor (GM-CSF)  Immune cell activator, supports APCs maturation.
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   PAP-GM-CSF antigenis cultured with patient’s APCs.
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   Patient’s APCsengulf 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.
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   After 2-3days, the fully mature APCs become PROVENGE®
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   In patient’sbody, Provenge activates the patient’s resting T Cells and induces their proliferation.
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   The Provenge-activatedT Cells are able to recognize, target and attack PAP antigen expressing prostate cancer cells.
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  At Phase 3clinical trial, Provenge showed a median OS (Overall Survival) benefit of 4.1 months compared with the placebo (P = 0.032).
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  MD Anderson's MoonShots Program
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   Launched byThe 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
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  COLORECTAL CANCER MOONSHOT They building a personalized vaccine for each individual patient. This vaccine is being used as a treatment, rather than for prevention.
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   Small pieceof tumor is removed How They Identify Personalized Targets
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   Sample issent to the lab and divided into 3 pieces.
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   Isolate DNAto identify mutations present in the tumor.
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   Isolate RNAto find out which of these mutations are expressed at the protein level.
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   Identify thetargets directly from the tumor.
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   All dataare integrated together using sophisticated bioinformatics to identify the top 10 targets for each patient, which then goes into the vaccine.
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   The vaccineis used alongside with Keytruda (Pembrolizumab) which is a PD-1 Inhibitor.
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  Stanford Cancer Vaccine
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   On January31 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.
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   The approachworked 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.
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   87 of90 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.
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  Oncolytic Viruses
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  Oncolytic Viruses  Someviruses 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.
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   2nd: whenthe cancer cells die, they release antigens into the body.
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  The immune systemtakes up those antigens, which alerts and activates T Cells to attack cancer through out the body.
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  Then T Cellsattack cancer through out the body.
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   On October2015 T-VEC (Imlygic®) - a modified version of herpes simplex virus (HSV) - was approved by FDA for treatment of melanoma.
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   Imlygic® hasbeen 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.
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  Thank You