Celebrating Our Patients. Immuno oncology Update An Exciting and Exploding Field. Megan Brafford May, PharmD, BCOP Ashley E. Glode, PharmD, BCOP

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1 Celebrating Our Patients Immuno oncology Update An Exciting and Exploding Field Megan Brafford May, PharmD, BCOP Ashley E. Glode, PharmD, BCOP 2 1

2 Objectives Outline the main mechanisms of action of immuno oncology agents Discuss the approved indications for each agent Identify side effects for immuno oncology agents Describe potential future indications for approved agents and agents in the development pipeline 3 The Basics 1 Immune system typically detects and destroys abnormal cells Cancer cells avoid detection by Reducing expression of tumor antigens on surface Expressing protein on surface to induce immune cell inactivation Inducing microenvironment to release substances that suppress immune responses and promote tumor cell proliferation and survival 1. National Cancer Institute. Immunotherapy: using the immune system to treat cancer. using immune system#1. 4 2

3 Immuno oncology: What Is It? 1,2 Increase strength of immune response against tumor Improve immune system s ability to recognize tumor Provide missing immune effector function Stimulate activities of specific components of immune system Counteract signals produced by cancer cells that suppress immune response 1. National Cancer Institute. Immunotherapy: using the immune system to treat cancer. using immunesystem#1. 2. Finn OJ. Immuno oncology: understanding the function and dysfunction of the immune system in cancer. Ann Oncol. 2012;23 Suppl 8:viii6 9. doi: /annonc/mds Immuno oncology Advantages Disadvantages Not cytotoxic Immune related adverse effect profile Durable responses Unique treatment response Slows tumor growth Low response rates 6 3

4 American Society of Clinical Oncology Advance of the Year 1 Several different strategies moved from bench to bedside Works against range of cancers Even more advanced tumors Potential to control tumor growth longer and with fewer adverse effects 1. Dizon DS, et al. Clinical cancer advances 2016: annual report on progress against cancer from the American Society of Clinical Oncology. J Clin Oncol. 2016;34(9): doi: /JCO Epub 2016 Feb 4. 7 Cancer Moonshot State of the Union Address: national moonshot initiative to eliminate cancer as we know it Accelerate research efforts and break down barriers to progress by enhancing data access and facilitating collaborations Research areas Prevention and Cancer Vaccine Development Early Cancer Detection Cancer Immunotherapy and Combination Therapy Genomic Analysis of Tumor and Surrounding Cells 1. The White House. Fact sheet: investing in the National Cancer Moonshot. press office/2016/02/01/fact sheet investing national cancer moonshot. Accessed 7/24/

5 Evolution of Treatment CAR=chimeric antigen receptor CSF 1R=colony stimulating factor 1 receptor CTLA 4=cytotoxic T lymphocyte antigen 4 IDO=indoleamine 2,3 dioxygenase PD 1=programmed death 1 PD L1=programmed death ligand 1 Source: Genentech: Cancer immunotherapy research is evolving to more targeted strategies. cancer research. Accessed 7/24/ Immuno oncology Immune Checkpoint Modulators Immune System Modulators Treatment Options Immune Cell Therapy Cancer Treatment Vaccines Therapeutic Antibodies 10 5

6 Cancer Treatment Vaccines: How They Could Work 1 Prime immune system to attack cancer cells Treat existing cancers by strengthening body s natural defenses against cancer Examples Dendritic cell vaccine Tumor cell vaccine Peptide/protein based vaccine Recombinant vector vaccine 1. National Cancer Institute. Immunotherapy: using the immune system to treat cancer. using immune system#1. 11 Cancer Treatment Vaccines 1,2 Approved Agent Sipuleucel T (Provenge ): prostate cancer Immune cells removed from patient s blood and sent to a lab Exposed to chemicals to create dendritic cells and exposed to protein called prostatic acid phosphatase (PAP) Dendritic cells given back to patient to produce immune response against prostate cancer cells Adverse Effects: infusion related reactions, fever, chills, back pain, fatigue, nausea Ongoing Research: combination therapy, timing of vaccine, use of booster vaccine 1. National Cancer Institute. Immunotherapy: using the immune system to treat cancer. using immune system#1. 2. U.S. National Institutes of Health: Clinical Trials. Cancer vaccine studies. [keyword search results]

7 Immune Checkpoint Modulators 1 Block immune checkpoint proteins Proteins limit strength and duration of immune responses Release breaks on immune system, increasing its ability to destroy cancer cells Examples: Cytotoxic T lymphocyte antigen 4 (CTLA 4) inhibitor Programmed cell death 1 (PD 1) inhibitor PD 1 receptor ligand (PD L1) inhibitor 1. National Cancer Institute. Immunotherapy: using the immune system to treat cancer. using immune system#1. 13 Mediators of T Cell Activation 1 APC: antigen presenting cells CTL: cytotoxic T lymphocyte 1. Chen DS, et al. Oncology meets immunology: the cancer immunity cycle. Immunity. 2013;39(1):

8 CTLA 4 Inhibitor 1 3 CTLA 4 Protein on some T cells that act as off switch to keep immune system in check CTLA 4 Inhibitor Attaches to CTLA 4 and stops it from working Boost body s immune response against cancer cells CD28: cluster of differentiation 28 HLA: human leukocyte antigen TCR: T cell receptor 1. Dizon DS, et al. Clinical cancer advances 2016: annual report on progress against cancer from the American Society of Clinical Oncology. J Clin Oncol. 2016: American Cancer Society. What s new in cancer immunotherapy research? new immuno res. 3. U.S. National Institutes of Health: Clinical Trials. CTLA 4 inhibitor studies. [keyword search results] CTLA 4 Inhibitor (continued) Approved Agents Ipilimumab (Yervoy ): melanoma Ongoing Research Combination therapy More tumor types: lung cancer, head and neck cancer, glioblastoma, prostate cancer, bladder cancer CD28: cluster of differentiation 28 HLA: human leukocyte antigen TCR: T cell receptor 1. Dizon DS, et al. Clinical cancer advances 2016: annual report on progress against cancer from the American Society of Clinical Oncology. J Clin Oncol. 2016: American Cancer Society (ACS). What s new in cancer immunotherapy research? whats new immuno res. 3. U.S. National Institutes of Health: Clinical Trials. CTLA 4 inhibitor studies. [keyword search results]

9 PD 1 and PD L1 Inhibitors 1,2 PD 1: checkpoint protein on T cells Normally acts as off switch to help keep T cells from attacking other cells in body Does this when it attaches to PD L1 protein on some normal and cancer cells When PD 1 binds to PD L1, this tells T cells to leave other cells alone Some cancer cells have large amounts of PD L1, which helps them evade immune attack Boost immune response against cancer cells 1. American Cancer Society (ACS). What s new in cancer immunotherapy research? whats new immuno res. 2. U.S. National Institutes of Health: Clinical Trials. PD 1 and PD L1 inhibitor studies. [keyword search results] PD 1 and PD L1 Inhibitor Mechanism 1 MHC=major histocompatibility complex TCR=T cell receptor 1. Dizon DS, et al. Clinical cancer advances 2016: annual report on progress against cancer from the American Society of Clinical Oncology. J Clin Oncol. 2016:

10 PD 1 and PD L1 Inhibitors (continued) 1,2 Approved Agents Nivolumab (Opdivo ) Pembrolizumab (Keytruda ) Atezolizumab (Tecentriq ) Ongoing Research Combination therapy Additional tumor types: nearly all solid tumors, leukemias, lymphomas 1. American Cancer Society (ACS). What s new in cancer immunotherapy research? whats new immuno res. 2. U.S. National Institutes of Health: Clinical Trials. PD 1 and PD L1 inhibitor studies. [keyword search results] Approved Indications for PD 1 and PD L1 Inhibitors BM1 Nivolumab Hodgkin lymphoma Melanoma Non small cell lung cancer Renal cell carcinoma Pembrolizumab Head and neck cancer Melanoma Non small cell lung cancer Atezolizumab Urothelial carcinoma 20 10

11 Slide 20 BM1 small square graphics boxes are not opening in PP Barbara Marino, 9/21/2016

12 Immune Related Adverse Effects (iraes) 1 1. West HJ. What are the potential side effects? (an immunotherapy primer for patients, pt. 4). December 2014: Global Resource for Advancing Cancer Education. treatments/2014/12/. 21 iraes Time Line 1 1. Weber JS, et al. Management of immune related adverse events and kinetics of response with ipilimumab. J Clin Oncol. 2012;30(21):

13 iraes Management 1 Provide counseling for prompt identification of moderate or severe iraes Rapid initiation of immunosuppression leads to favorable outcomes Withhold treatment and do not resume until toxicity returns to grade 1 iraes management options initiate corticosteroids 0.5 to 2 mg/kg/day of prednisone equivalent Infliximab Mycophenolate mofetil (MMF) Cyclophosphamide Supportive care and symptom management 1. Weber JS, et al. Management of immune related adverse events and kinetics of response with ipilimumab. J Clin Oncol. 2012;30(21): iraes Monitoring 1 Reduction in tumor growth Liver function tests Serum creatinine Thyroid function tests S/S pneumonitis S/S colitis 1. Weber JS, et al. Management of immune related adverse events and kinetics of response with ipilimumab. J Clin Oncol. 2012;30(21):

14 Immune Cell Therapy 1 Adoptive Cell Transfer (ACT) Tumor infiltrating lymphocytes (TILs) Collect lymphocytes that have infiltrated a patient s tumor Grow cells that show greatest recognition of tumor cells Activate with cytokines and reinfuse into the patient Increase amount of cells with ability to target tumor 1. National Cancer Institute. Immunotherapy: using the immune system to treat cancer. using immune system#1. 25 Immune Cell Therapy (continued) 1 Chimeric antigen receptor (CAR) T cell therapy Collect patient s T cells Genetically modify to express protein called chimeric antigen receptor (CAR) on T cells Multiply in lab and reinfuse into the patient CAR T cells attach to specific proteins on surface of cancer cells Once bound, CAR T cell becomes activated and attacks cancer cells 1. National Cancer Institute. Immunotherapy: using the immune system to treat cancer. usingimmune system#

15 CAR T Cell Therapy Mechanism 1 MHC: major histocompatibility complex TCR: T cell receptor scfv: single chain variable fragment CAR: chimeric antigen receptors 1. Lee DW, et al. The future is now: chimeric antigen receptors as new targeted therapies for childhood cancer. Clin Cancer Res. 2012;18(10): CAR T Cell Therapy Toxicity 1 Ranges from mild to severe, life threatening adverse effects Therapy administered inpatient for monitoring and management of toxicities Adverse effects Cytokine release syndrome (CRS) Encephalopathy B cell aplasia Treatment options Tocilizumab Vasoactive pressors Antiepileptics Antipyretics 1. Brudno JN, et al. Toxicities of chimeric antigen receptor T cells: recognition and management. Blood. 2016;127(26):

16 Therapeutic Antibodies 1 Unconjugated Monoclonal Antibodies (mabs) Signaling mediated by cross linking of surface antigen causing cells to commit suicide (apoptosis) Block an activation signal needed for continued cell growth Antibody dependent cellular cytotoxicity (ADCC): recruit cytotoxic cells (monocytes and macrophages) Complement mediated cytotoxicity (CMC): bind complement leading to direct cell toxicity Approved Agents Too many to name! 1. National Cancer Institute. Immunotherapy: using the immune system to treat cancer. using immune system#1. 29 Therapeutic Antibodies (continued) 1 Antibody Drug Conjugates (ADCs) Created by chemically linking antibodies or fragments of antibodies to a toxic substance Toxic substances: poison (bacterial toxin), small molecule drug, radioactive compound Antibody portion of ADC binds to target expressed on surface of cancer cells Once bound, taken up by cell and toxic substance kills cell Approved Agents Ado trastuzumab emtansine (Kadcyla ): breast cancer Brentuximab vedotin (Adcetris ): Hodgkin lymphoma, anaplastic large T cell lymphoma Ibritumomab tiuxetan (Zevalin ): Non Hodgkin s lymphoma 1. National Cancer Institute. Immunotherapy: using the immune system to treat cancer. using immunesystem#

17 ADCs 1 1. Carter PJ, et al. Antibody drug conjugates for cancer therapy. Cancer J. 2008;14(3): Bispecific T Cell Engaging Antibody (BiTE) 1 Made up of 2 different mabs Attach to 2 different proteins at same time CD19 and CD3 Approved Agent Blinatumomab (Blincyto ) Acute lymphoblastic leukemia CD19 1. Wu J, et al. Blinatumomab: a bispecific T cell engager antibody against CD19/CD3 for refractory acute lymphoid leukemia. J Hem/Onc. 2015;8(104):

18 Therapeutic Antibodies 1 Adverse Effects: infusion related reactions, chills, fever, immunosuppression, fatigue ADCs: neuropathy, skin rash BiTE Antibody: edema, neurotoxicity, headache, skin rash, febrile neutropenia, CRS Ongoing Research: Nononcologic uses Combination therapy Maintenance therapy Timing of therapy 1. U.S. National Institutes of Health: Clinical Trials. Therapeutic antibody studies for cancer. [keyword search results]. ClinicalTrials.gov. Accessed 8/31/ Immune System Modulators 1 Use proteins that normally help regulate or modulate immune system activity to enhance body s immune response against cancer Given by themselves or as adjuvants Cytokines: chemicals made by some immune system cells Control growth and activity of other immune system cells and blood cells 1. American Cancer Society (ACS). What s new in cancer immunotherapy research? whats new immuno res

19 Immune System Modulators (continued) 1 Approved Agents Interferon alpha: leukemia, melanoma Helps body resist viral infections and cancers Boosts ability of certain immune cells to attack cancer cells Directly slows growth of cancer cells, and blood vessels Interleukin 2 (IL 2): melanoma, renal cell carcinoma Helps immune system cells grow and divide more quickly Talimogene laherparepvec (Imlygic ): melanoma Oncolytic virus modified to make GM CSF to boost immune response 1. American Cancer Society. What s new in cancer immunotherapy research? whats new immuno res. 35 Immune System Modulators (continued) 1 Interferon alpha Adverse Effects: headache, fatigue, rigors, insomnia, alopecia, nausea, vomiting, neutropenia, increased liver function tests, weakness, myalgias, arthralgias, fever Ongoing Research: combination therapy, primarily melanoma, renal cell, leukemia, hepatocellular carcinoma, and nononcologic disease states Interleukin 2 (IL 2) Adverse Effects: capillary leak syndrome (hypotension, edema, increased serum creatinine), fever, chills, confusion, malaise, weakness, skin rash, diarrhea Ongoing Research: combination therapy, dosing strategy, leukemia, lymphoma, graft versus host disease, melanoma, renal cell cancer, neuroblastoma Talimogene laherparepvec (Imlygic ) Adverse Effects: fatigue, chills, nausea, vomiting, diarrhea, injection site pain, flu like symptoms Ongoing Research: combination therapy, melanoma, breast cancer, sarcoma 1. U.S. National Institutes of Health: Clinical Trials. Immune system modulators. [keyword search results]. ClinicalTrials.gov. Accessed 8/31/

20 Combination Therapy 1 1. Vanneman M, et al. Combining immunotherapy and targeted therapies in cancer treatment. Nature Reviews Cancer. 2012;12: Combination Therapy 1 1. Sharma P, et al. Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential. Cell. 2015;161(2):

21 Future What s Next? 1 Cancer Treatment Vaccines Need better understanding of basic biology underlying how immune system cells and cancer cells interact New imaging techniques to observe interaction of killer T cells and cancer cells Identify mechanisms of cancer cell evasion or suppression of anticancer immune response 1. National Cancer Institute. Cancer vaccines fact sheet. cancer/causes prevention/vaccines fact sheet#q Future What s Next? (continued) 1 Cancer Treatment Vaccines Areas of research Identification of novel cancer associated antigens or neoantigens that may be more effective in stimulating immune response Early phase clinical trials testing neoantigen based personalized vaccine for patients with glioblastoma and melanoma Development of methods to enhance ability of cancer associated antigens to stimulate immune system Determine how to combine multiple antigens within a single cancer treatment vaccine to maximize immune response 1. National Cancer Institute. Cancer vaccines fact sheet. cancer/causes prevention/vaccines fact sheet#q

22 Future What s Next? (continued) 1 Cancer Treatment Vaccines Agents in development Dendritic cell vaccines: renal cell carcinoma, glioblastoma, prostate cancer Autologous tumor cell vaccines: colorectal cancer, follicular lymphoma Anti idiotype vaccines: lymphomas and some solid tumors Allogeneic vaccines: lung cancer DNA based vaccines: metastatic breast cancer 1. National Cancer Institute. Cancer vaccines fact sheet. cancer/causes prevention/vaccines fact sheet#q Future What s Next? (continued) 1 Immune Checkpoint Modulators Need better understanding why checkpoint inhibitors are effective in some patients and not others Areas of research Identifying ways to expand use in other cancers Combination therapy PD 1 and CTLA 4 inhibition, combination with chemotherapy 1. National Cancer Institute. Immunotherapy: using the immune system to treat cancer. using immune system#

23 Future What s Next? (continued) 1,2 Immune Checkpoint Modulators Agents in development: Anti GITR (glucocorticoid induced tumor necrosis factor [TNF] receptor) antibody: enhance immune system response by enabling T cells to be more effective in attacking cancer cells IDO (indoleamine 2,3 dioxygenase) inhibitor: prevents tumor invasion of immune system by preventing tryptophan depletion and starvation of cytotoxic T cells within tumor microenvironment LAG 3 (lymphocyte activation gene 3) antibody: given with PD 1 inhibitor to work together to suppress antitumor T cell immune response and restore T cells to full function resulting in stronger antitumor immunity 4 1BB also known as CD137 antibody: costimulatory agent for activated T cells; stimulates first wave of antitumor reaction OX40 (CD134) agonist: augments T cell differentiation and cytolytic function leading to enhanced antitumor immunity against tumors TIM3 (T cell immunoglobulin mucin 3) antibody: block cell surface receptor on effector T cells to produce tumor regression 1. Mulvey A. Immune checkpoint inhibitors: what s next? publications/our blog/february 2015/immune checkpoint inhibitors whats next. 2. Sheridan C. IDO inhibitors move center stage in immuno oncology. Nat Biotechnol. 2015;33(4): doi: /nbt Future What s Next? (continued) 1 3 Immune Cell Therapy CAR T Cell Therapy Need to improve management of side effects, identify appropriate patients, refine production process TILs Need to improve methods of obtaining TILs from patients Areas of Research CAR T Cell Therapy: development of better receptors and identification of better targets TILs: application in melanoma and other solid tumors 1. American Cancer Society. What s new in cancer immunotherapy research? whats new immuno res. 2. National Cancer Institute. CAR T cell therapy: engineering patients' immune cells to treat their cancers. cancer/treatment/research/car t cells. Accessed 8/11/ Kontermann RE. Bispecific antibodies. New Monoclonal antibody developed that can target proteins inside cancer cells. releases/new monoclonalantibody developed can target proteins inside cells. 4. National Institutes of Health. Clinical Trials. Immune cell therapy. [keyword search results]. ClinicalTrials.gov. Accessed 8/31/

24 Future What s Next? (continued) 1 3 Therapeutic Antibodies Need to decrease immunogenicity and adverse effects, develop using parts of antibodies to increase efficacy, continue to create bispecific antibodies Areas of Research Combination therapy New targets New and radiolabeled ADCs Bispecific antibodies 1. American Cancer Society. What s new in cancer immunotherapy research? new immuno res. 2. National Cancer Institute. CAR T cell therapy: engineering patients' immune cells to treat their cancers. cancer/treatment/research/car t cells. Accessed 8/11/ Kontermann RE, et al. Bispecific antibodies. Memorial Sloan Kettering Cancer Center. New monoclonal antibody developed that can target proteins inside cancer cells. releases/new monoclonal antibody developed can target proteins inside cells. 4. National Institutes of Health. Clinical Trials. Therapeutic antibodies. [keyword search results]. ClinicalTrials.gov. Accessed 8/31/ Future What s Next? (continued) 1 4 Agents in development ESK1 antibody: targets protein called WT1 inside cancer cells IMMU132: ADC with SN38 as toxin attached to TROP2 inhibitor Catumaxomab: trifunctional bispecific antibody Anti EpCAM x Anti CD3 AFM13: tetravalent bispecific antibody CD30 + CD16 1. American Cancer Society. What s new in cancer immunotherapy research? new immuno res. 2. National Cancer Institute. CAR T cell therapy: engineering patients' immune cells to treat their cancers. cancer/treatment/research/car t cells. Accessed 8/11/ Kontermann RE. Bispecific antibodies. New monoclonal antibody developed that can target proteins inside cancer cells. releases/new monoclonal antibodydeveloped can target proteins inside cells. 4. National Institutes of Health. Clinical Trials. Therapeutic antibodies. [keyword search results]. ClinicalTrials.gov. Accessed 8/31/

25 Future What s Next? (continued) 1,2 Immune System Modulators Need to improve upon side effects of interferon and IL 2 Need better understanding of tumor biology and virology to maximize efficacy Areas of Research Combination therapy Utilizing different viruses Altering host immune response to virus to prevent immune system from targeting virus Agents in Development GL ONC1: oncolytic vaccinia virus (Lister strain used as vaccine against smallpox) Ad5 ycd/muttksr39rep hil12: oncolytic adenovirus mediated cytotoxic and IL 12 gene therapy HSV1716: oncolytic herpes simplex virus 1. National Institutes of Health. Clinical Trials. Immune system modulators. [keyword search results]. ClinicalTrials.gov. Accessed 8/31/ Wong HH, et al. Oncolytic viruses for cancer therapy: overcoming the obstacles. Viruses. 2010;2(1): doi: /v Learning Objectives Outline the main mechanisms of action of immuno oncology agents Discuss the approved indications for each agent Identify side effects for immuno oncology agents Describe potential future indications for approved agents and agents in the development pipeline 48 24

26 References National Cancer Institute (NCI). Immunotherapy: using the immune system to treat cancer. using immune system#1. Updated 9/14/2015. Finn OJ. Immuno oncology: understanding the function and dysfunction of the immune system in cancer. Annals of Oncology. 2012;23(S8):viii6 viii9. Dizon DS, Krilov L, Cohen E, et al. Clinical Cancer Advances 2016: annual report on progress against cancer from the American Society of Clinical Oncology. Journal of Clinical Oncology. 2016;34: The White House Office of the Press Secretary. Fact Sheet: Investing in the National Cancer Moonshot. pressoffice/2016/02/01/fact sheet investing national cancer moonshot. Updated 2/1/2016. Accessed 7/24/2016. Research Cancer Immunotherapy. Cancer immunotherapy research is evolving to more targeted strategies. cancer research. Accessed 7/24/2016. Clinical Trials. Chen DS, et al. Oncology meets immunology: the cancer immunity cycle. Immunity. 2013:39(1):1 10. American Cancer Society (ACS). What s new in cancer immunotherapy research?. whats new immuno res. Updated 11/5/2015. West HJ. What are the potential side effects? (an immunotherapy primer for patients, pt. 4). treatments/2014/12/. Updated 12/30/2014. Weber JS, et al. Management of immune related adverse events and kinetics of response with ipilimumab. JCO. 2012;30(21): Lee DW, et al. The future is now: chimeric antigen receptors as new targeted therapies for childhood cancer. Clin Cancer Res. 2012;18(10): Brudno JN, et al. Toxicities of chimeric antigen receptor T cells: recognition and management. Blood. 2016:127(26): American Society of Clinical Oncology. Clinical cancer advances progress/reports studies/clinical cancer advances#/advanceyear cancer immunotherapy. Carter PJ, et al. Antibody drug conjugates for cancer therapy. Cancer J. 2008;14(3): Wu J, et al. Blinatumomab: a bispecific T cell engager antibody against CD19/CD3 for refractory acute lymphoid leukemia. J Hem/Onc. 2015;8(104):1 7. Vanneman M, et al. Combining immunotherapy and targeted therapies in cancer treatment. Nature Reviews Cancer. 2012;12: Sharma P, et al. Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential. Cell. 2015;161(2): National Cancer Institute. Cancer vaccines fact sheet. cancer/causes prevention/vaccines fact sheet#q13. Mulvey A. Immune checkpoint inhibitors: what s next? publications/our blog/february 2015/immune checkpoint inhibitorswhats next. Updated 2/9/2016. Sheridan C. IDO inhibitors move center stage in immuno oncology. Nature Biotechnology. 2015;33(4): Linch SN, McNamara MJ, Redmond WL. OX40 agonists and combination immunotherapy: putting the pedal to the metal. Frontiers Oncol. 2015;5(34):1 14. National Cancer Institute (NCI). CAR T cell therapy. Engineering patients immune cells to treat their cancers. t cells. Updated 10/16/2014. Kontermann RE, Brinkmann U. Bispecific antibodies. Drug Discovery Today. 2015;20(7): MSKCC. New monoclonal antibody developed that can target proteins inside cancer cells. releases/new monoclonal antibodydeveloped can target proteins inside cells. Wong HH, Lemoine NR, Wang Y. Oncolytic viruses for cancer: overcoming the obstacles. Viruses. 2010;2:

27 Questions 51 Celebrating Our Patients 26