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Vaccine for Cancer Immunotherapy - Creative Biolabs
- 1. © 2023 CREATIVE BIOLABS Vaccine for Cancer Immunotherapy www.creative-biolabs.com
- 2. © 2023 CREATIVE BIOLABS Content Introduction to Cancer Vaccines History of tumor antigens and cancer vaccines Different types of tumor antigens Formulations of cancer vaccines Tumor-immune cycle induced by cancer vaccines Mechanism of cancer vaccines Resistance of cancer vaccines Customizing a patient-specific cancer vaccine Basic neoantigen vaccine pipeline Key clinical trials of personalized neoantigen-based cancer vaccines Approved vaccines for cancer prevention and therapy Mechanism of Cancer Vaccines Creative Biolabs’ Cancer Vaccine Development Solutions Cancer Vaccines in Clinic 02 Vaccine for Cancer Immunotherapy
- 3. © 2023 CREATIVE BIOLABS Introduction to Cancer Vaccines 1893 1973 1991 1993 2009 2010 2012 2015 2017 Cancer treatment with bacterial toxins Discovery of dendritic cells Discovery of the first human tumor-associated antigen: MAGE1 GM-CSF-secreting tumor cell vaccination in mice First FDA approval for a Therapeutic cancer vaccine (Sipuleucel-T) Clinical response to vaccination with synthetic long peptides from HPV-16 viral oncoproteins in patients with vulvar intraepithelial neoplasia Improved overall survival shown after vaccination with IMA901, a multi- peptide vaccine for renal cell cancer Extended survival after vaccination with a GVAX prime and a mesothelin-expressing Listeria monocytogenes boost for pancreatic cancer NeoVax, a synthetic long- peptide neoantigen vaccine for melanoma DC-based vaccine pulsed with personal melanoma neopeptides History of tumor antigens and cancer vaccines IVAC MUTANOME, an mRNA neoantigen vaccine for melanoma 03 INTRODUCTION OF CANCER VACCINES
- 4. © 2023 CREATIVE BIOLABS Formulations Pros (+) Cons (-) · Whole tumor cell · Tumor lysate · Antigen-presenting cell - High immunogenicity - Control of antigen presentation - Expensive and difficult to produce - Risk of leukapheresis (vascular injury, electrolyte imbalance) · Protein · Peptide - Low toxicity - Easy to produce - Low/moderate immunogenicity - Peptide-based: restricted to the HLA subtype - Protein-based: expensive to produce · Virus · Bacterium - High immunogenicity - Easy to produce on large scale - Potential high toxicity - Risk of undesired infections - Immune response against the vector · DNA · RNA - Easy delivery of multiple antigens - Induction of cellular and humoral immunity - Not restricted to HLA- patient type - RNA vaccines: specific transportation/storage condition required - DNA and RNA vaccines: pooly immunogenic in humans Introduction to Cancer Vaccines Formulations of cancer vaccines Class of tumor antigen Description Tumor specificity Example of tumor antigen Tumor Specific Antigens (TSA) · Cancer germline antigens - Expression on healthy cells limited to testes, fetal ovaries and trophoblasts - Expressed on a wide a variety of cancer types High MAGE, NY-ESO-1, GAGE, BAGE · Tumor specific mutated antigens - Mutations resulting in the generation of a new peptide - Mutations can be generated at the gene level, from chromosome translocations or due post translational modification High KRAS, p53, NRAS, BCR-ABL translocation, ETV6, NPM/ALK, ALK · Oncogenic viral antigens - Abnormal expression on cells infected with an oncovirus. High EBV LMP-1/LMP- 2A, HPV E6/E7, HTLV-1 Tax Tumor associated Antigens (TAA) · Tissue differentiation antigens - Antigen expressed on tumor cells and normal cells Low Melan A/MART-1, gp100, Tyrosinase, PSA, CEA · Overexpressed antigens - Antigen overexpressed on tumor cells and normal level of expression on healthy cells Low HER2, hTERT, p53, Survivin, MUC1, WT1, cyclin B Different types of tumor antigens 04 INTRODUCTION OF CANCER VACCINES
- 5. © 2023 CREATIVE BIOLABS Mechanism of Cancer Vaccines 05 MECHANISM OF CANCER VACCINES Tumor-immune cycle induced by cancer vaccines (Liu, 2021)
- 6. © 2023 CREATIVE BIOLABS Mechanism of Cancer Vaccines 06 MECHANISM OF CANCER VACCINES Mechanism of cancer vaccines (Liu, 2021)
- 7. © 2023 CREATIVE BIOLABS Mechanism of Cancer Vaccines 07 MECHANISM OF CANCER VACCINES Resistance of cancer vaccines (Liu, 2021)
- 8. © 2023 CREATIVE BIOLABS Cancer Vaccines in Clinic Tumor Normal Diagnosis Biosample acquisition Comparative sequencing Mutation identification Target prioritization Vaccine design and production Administration of vaccine Customizing a patient-specific cancer vaccine 08 CANCER VACCINES IN CLINIC (Sahin, 2018)
- 9. © 2023 CREATIVE BIOLABS Sample collection DNA/RNA Healthy tissue Blood Tumor biopsy SNV Deletion Insertion Intron retention Tumor-specific non- synonymous mutations Whole-exome & Transcriptome sequencing HLA-types 4-digit HLA-typing Neoantigen vaccine formulation Predicted Neoantigens HLA-specific peptides A C APC MHC 1 TCR Cytokines T cells Barcode sequencing Sorting of positive T cells Patient T cells Neoantigen validation DNA-barcoded pHLA multimers Barcode Barcode Barcode B Ex vivo activation/proliferation assay Mutated Wild-type Selection of transcribed sequences AAAA AAAA Basic neoantigen vaccine pipeline Cancer Vaccines in Clinic 09 CANCER VACCINES IN CLINIC (Tay, 2019)
- 10. © 2023 CREATIVE BIOLABS Trial Phase Tumor type Vaccine format Key contributions NCT00683670 I Advanced-stage melanoma Dendritic cell Provide proof of concept that neoantigen vaccines can induce T cell responses NeoVax (NCT01970358) I/Ib Resected high-risk stage III/IV melanoma Peptide Demonstrate that neoantigen peptide- based vaccines can induce CD4+ T cell and CD8+ T cell responses and can be combined with ICIs IVAC MUTANOME (NCT02035956) I NY-ESO-1-positive and/or tyrosinase- positive stage III or IV melanoma mRNA Demonstrate that mRNA vaccines incorporating TAAs and neoantigens can induce CD4+ T cell and CD8+ T cell responses and can be combined with ICIs NeoVax (NCT02287428) I/Ib MGMT promoter unmethylated glioblastoma Peptide Demonstrate that neoantigen vaccines can induce CD4+ T cell and CD8+ T cell responses in immunologically cold tumors with low mutational burdens GAPVAC (NCT02149225) I Glioblastoma Peptide Demonstrate that peptide vaccines incorporating TAAs and neoantigens can induce CD4+ T cell and CD8+ T cell responses in immunologically cold tumors with low mutational burdens Key clinical trials of personalized neoantigen- based cancer vaccines Cancer Vaccines in Clinic 10 CANCER VACCINES IN CLINIC
- 11. © 2023 CREATIVE BIOLABS Vaccine Target antigen Application Cancer type · Hepatitis B Hepatitis B virus (HBV) surface antigen (HBsAg) Preventative Hepatocellular carcinoma caused by chronic HBV infection · Cervarix · Gardasil-4 · Gardasil-9 L1 protein of different human papilloma virus (HPV) types Preventative HPV-associated cervical, oropharyngeal, anal, penile, and vulvovaginal cancers · Bacillus Calmette- Guerin (BCG) Non-pathogenic Mycobaterium bovis Therapeutic High-risk non-muscle-invasive bladder cancer (NMIBC) · Sipuleucel-T (Provenge) Prostate acid phosphatase protein Therapeutic Castration-resistant prostatic cancer Cancer Vaccines in Clinic 11 CANCER VACCINES IN CLINIC Approved vaccines for cancer prevention and therapy
- 12. © 2023 CREATIVE BIOLABS Cancer Vaccine Discovery Cancer Vaccine Engineering Cancer Vaccine Analytical Characterization Cancer Vaccine In Vivo Assessment Cancer Vaccine GMP Manufacturing Creative Biolabs’ One-stop Cancer Vaccine Solutions 12 CREATIVE BIOLABS’ ONE-STOP CANCER VACCINE SOLUTIONS
- 13. © 2023 CREATIVE BIOLABS Vaccine for Cancer Immunotherapy www.creative-biolabs.com info@creative-biolabs.com