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Vaccine for Cancer Immunotherapy - Creative Biolabs
- 1. © 2023 CREATIVEBIOLABS Vaccine for Cancer Immunotherapy www.creative-biolabs.com
- 2. © 2023 CREATIVEBIOLABS 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 CREATIVEBIOLABS 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 CREATIVEBIOLABS 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 CREATIVEBIOLABS Mechanism of Cancer Vaccines 05 MECHANISM OF CANCER VACCINES Tumor-immune cycle induced by cancer vaccines (Liu, 2021)
- 6. © 2023 CREATIVEBIOLABS Mechanism of Cancer Vaccines 06 MECHANISM OF CANCER VACCINES Mechanism of cancer vaccines (Liu, 2021)
- 7. © 2023 CREATIVEBIOLABS Mechanism of Cancer Vaccines 07 MECHANISM OF CANCER VACCINES Resistance of cancer vaccines (Liu, 2021)
- 8. © 2023 CREATIVEBIOLABS 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 CREATIVEBIOLABS 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 CREATIVEBIOLABS 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 CREATIVEBIOLABS 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 CREATIVEBIOLABS 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 CREATIVEBIOLABS Vaccine for Cancer Immunotherapy www.creative-biolabs.com [email protected]