Transcript Innovations in Cancer Treatment - Idaho Society of Health

Innovations in Cancer
Treatment
Stephanie Magdanz, PharmD, BCOP
Oncology Clinical Pharmacist
Boise VA Medical Center
March 6, 2016
Disclosures
 Stephanie Magdanz, PharmD, BCOP reports having no
financial or advisory relationships with corporate
organizations
Learning Objectives
 Recognize the disadvantages & challenges of
traditional cancer therapies.
 Explain how monoclonal antibodies stimulate
the immune system to attack cancer cells.
 Summarize the process of CAR-T therapy.
 Describe how viruses can be used to treat
cancer.
Cancer Statistics
 In the U.S., 1 of every 2 men and 1 of every 3 women in will receive a
cancer diagnosis in their lifetime
 Cancer is the #2 cause of death in the United States
• Projected to surpass heart disease as #1 in the next decade
 Cancer is the #1 cause of death in Idaho
 Cancer is the #1 cause of death by disease in children
• Every 3 minutes, somewhere in the world, a child is diagnosed with
cancer
 There are now >14 million cancer survivors in the U.S.
• 5-year survival for all cancers is >68% (2004-2010) up from 49% in
the late 1970s
 The FDA approved 18 new cancer drugs in 2015 compared to 6 in 2010
 Currently 800 ongoing clinical trials for new cancer immunotherapy
drugs; only 5% of cancer patients participate in clinical trials
 Cancer spending is roughly 5% of the total spent on medical care in the
U.S in general
www.cdc.gov, www.strongagainstcancer.org, Sweeney N, et al. Boston Healthcare. May 2015.
Cancer Statistics
www.cdc.gov
Cancer Statistics
www.cdc.gov
History of Cancer Treatment
 1550 BC – Egyptian papyrus written by Imhotep is the first
documentation of cancer
 460 BC – Hippocrates “names” cancer using the terms carcinos
& carcinoma from the Greek word for crab
 160 AD – Medical conditions were explained by the four
humors (blood, black bile, yellow bile, white bile)
 1775 – British surgeon Percival Pott reported increased
scrotum cancer among chimney sweeps
 1846/1865 – Anesthesia & antiseptic (carbolic acid) discovered
 1878 – Paul Erlich discovers the principle of what will later be
known as chemotherapy
 1895 – Discovery of x-ray & experiments in treating cancer
 1937 – National Cancer Institute Act signed by President
Roosevelt
History of Cancer Timeline www.cancerfilms.org, The History of Cancer www.cancer.org
History of Cancer Treatment
 1941 – WWII soldiers exposed to mustard gas found to have toxic
changes to bone marrow
• Led to development of alkylating agents in 1943 at Yale
 1945 – American Cancer Society founded
 1948 – Sidney Farber, the “father of chemotherapy” used
aminopterin (methotrexate) to treat leukemia patients
 1952 – Screening being done using pap smear, colonoscopy &
mammography
 1955 – Marlboro Man ad campaign; sales up 5000% over 8 months
 1956 – First bone marrow transplant done in leukemia patient
 1957 – US Surgeon General report that cigarette smoking is
causative factor in lung cancer
 1969/1971 – War on Cancer; Nixon signs National Cancer Act
 1976 – Mammogram Screening Trial results in 20% reduction in
deaths for women >55
History of Cancer Timeline www.cancerfilms.org, The History of Cancer www.cancer.org
History of Cancer Treatment
 1982 – High-dose chemo + autologous HSCT in solid tumors;
found to have no benefit by late 1990s
 1992 – Breast cancer HER-2 gene identified
 1999 – Imatinib (Gleevec®) trial – launch of targeted therapies
 2003 – Human Genome Project completed – map of entire
sequence of human DNA
 2006 – Cancer Genome Atlas – gene sequencing of tumors
 2010 – President’s Cancer Panel – increased research
 2011 – Emphasis on Oncology immunotherapy research (ie:
ipilimumab for malignant melanoma)
 2015 – President Obama’s “Moonshot to Cure Cancer” – calls
for expanded funding & screening, increased access to clinical
trials, insurance coverage of gene testing, decreased
prescription drug prices, & sharing of information
History of Cancer Timeline www.cancerfilms.org, The History of Cancer www.cancer.org, “Moonshot” article
www.healthline.com
Cancer Treatment:
Drawbacks & Challenges
 Surgery, radiation & chemotherapy
• Not all patients who need the treatment are eligible
• Considerable adverse effects including death, pain, infections,
heart failure, fatigue, nausea/vomiting, etc
• Long-term sequelae – heart failure, pulmonary, secondary cancers
• Some cancer cells may survive causing progression or recurrence
 Tumor resistance
• Immune system has a critical role in cancer pathogenesis (ie:
immunocompromised patients)
• Solid organ transplant – 2-fold increase in solid tumors & 20fold increase in skin cancer, lymphoma & sarcomas
• HIV – 40% of AIDS patients develop cancer
• Tumors consist mainly of normal tissue components (self)
Cancer immunotherapy www.dendreon.com, BiTE antibodies www.amgenoncology.com
Cancer Treatment:
Drawbacks & Challenges
 Tumor resistance (cont.)
• Immune system is trained to avoid attacking itself
• Cytotoxic T lymphocytes (CTLs) recognize tumor antigens, bind &
cause tumor cell lysis
 Problem – tumors can evade T cell recognition (escape phase)
• Immune system exhaustion
• Tumor growth is too fast for immune system to keep up
• Checkpoints on the T cell (CTLA-4 & PD-1) are upregulated
causing the T cell to turn off
• Tumors can secrete immunosuppressive cytokines
 Solution – the new era of cancer treatment
• Encourage immune cells that recognize tumor
• Help immune system track down wandering cancer cells & destroy
them
• Develop tumor specific Ab’s outside the body & inject them into
patients
Cancer immunotherapy www.dendreon.com, BiTE antibodies www.amgenoncology.com
Cancer Treatment: A New Era
 Cytokines – T cell growth factors that stimulate immune response
(ie: interferons, interleukins)
 Allogeneic HSCT – tumor cells eliminated through high-dose
chemotherapy followed by graft-versus-tumor effect
 Monoclonal Antibodies – direct or indirect immune response
• Rituximab – immune-mediated cytotoxic response
• Trastuzumab & cetuximab – block signal pathways needed for
cell growth
• Bevacizumab – block angiogenesis needed for oxygen &
nutrients
• Brentuximab vedotin – antibody drug conjugate (ADC)
combining a monoclonal Ab with cyctotoxic drug
• Tositumomab 131I – antibody combined with radioactive
particle
 Oral molecular target drugs (aka tyrosine kinase inhibitors, signal
transduction inhibitors, “nibs”)
Cancer immunotherapy www.dendreon.com
Monoclonal
Antibodies
Trastuzumab
Bevacizumab
Cetuximab
Panitumumab
Tipifarnib
Lonafarnib
Erlotinib
Imatinib
Lapatinib
Small
Molecule
TKIs/STIs
Hudis CA. NEJM 2007;357(1):41
Sorafenib
mTOR
LoRusso P M et al. Clin Cancer Res 2011;17:6437-6447
Cancer Treatment: A New Era
 Autologous cellular immunotherapy – activated APCs are
reinfused into patient to direct immune cells vs tumor cell
(ie: sipuleucel-T)
 Immune checkpoint inhibitors – “release the brakes” on
the immune system (ie: ipilimumab, nivolumab,
pembrolizumab)
 CAR-T therapy – chimeric antigen receptor (CAR) T cells
 Immunovirus – therapeutic cancer vaccine
 Future directions – BiTE antibodies, DNA methylation
signature, TMEM score, magic wands, IDH2 blockers,
proteomics, intraoperative radiation, CRISP-R technology
Cancer immunotherapy www.dendreon.com
Patient Case #1: PD-1 Inhibitor
 ED 33yo male with Hodgkins Lymphoma
 Apr 2011: standard chemo w/ ABVD (doxorubicin,
bleomycin, vinblastine, dacarbazine) x6 cycles
 2nd line chemo: GDP (gemcitabine, dexamethasone,
cisplatin)
 2012: autologous stem cell transplant → recurrence
 Salvage chemo: brentuximab vedotin (Adcetris®)
 Salvage chemo: GDP, MOPP (mechlorethamine,
vincristine, procarbazine, prednisone), bendamustine
 Dec 2014: allogeneic stem cell transplant → recurrence
 Now what???
Patient Case #2: CAR-T Therapy
 JA 3yo male with Acute Lymphocytic Leukemia
(ALL)
 2013 – diagnosed at age 18 months
 2 year battle chemotherapy → relapsed twice
 Allogeneic stem cell transplant → relapse
 Out of treatment options other than hospice
 Now what???
Strongagainstcancer.org
Patient Case #3: Immunovirus
 SL 20yo female with tennis ball sized GBM
(glioblastoma multiforme) brain tumor
 2011 – surgery; 98% removed
 Radiation & chemotherapy (temozolamide)
 Recurrence 2012 → 1st patient on Phase I Polio
immunovirus trial at Duke University
 Treatment began in May → tumor is larger by June
 What happened next???
60 Minutes: Killing Cancer Part 1 & 2, Mar 29, 2015. Available at www.cbsnews.com
Immunotherapy:
Checkpoint inhibitors
 Immune system relies on multiple checkpoints to
avoid over activation on healthy cells
 Tumor cells hijack these checkpoints to escape
detection
 CTLA-4 & PD-1 are upregulated on T cell surface in
some cancers
 PD-L1 can be expressed on tumor cells
endogenously or induced by association with T cells
 PD-1:PD-L1 interaction results in T cell suppression
(anergy, exhaustion, death)
Atkins MB et al. Clinical Care Options slideset 2014.
IPILIMUMAB
NIVOLUMAB
PEMBROLIZUMAB
Drake CG et al. Nat Rev Clin Onc. 2014;11:24-37.
Immunotherapy:
Checkpoint inhibitors
 In melanoma, renal cell, & other tumors, PD-L1
expression is associated with more aggressive
disease
 Inhibiting CTLA-4 & PD-1 can “release the brakes”
 Checkpoint inhibitors don’t attack the tumor, they
set the T cells straight
 Activity powerful enough to work in the CNS – T cells
go everywhere
 Melanoma patients – on MRI, brain mets are
surrounded by tons of T cells
Atkins MB et al. Clinical Care Options slideset 2014.
Immunotherapy:
Checkpoint blockade
Priming phase
(lymph node)
Effector phase
(peripheral tissue)
T-cell migration
Dendritic
cell
MHC
MHC
TCR
TCR
CD28
CD28
Dendritic
cell
T cell
B7
CTLA-4
CTA-4
Ribas A. N Engl J Med. 2012;366:2517-2519.
Cancer
cell
T cell
T cell
T cell
MHC
MHC
PD-1
PD-1
PD-L1
PD-L1
Cancer
cell
Immunotherapy: PD-1 inhibitors
 Nivolumab (Opdivo®) – FDA approval
• Melanoma – unresectable or metastatic; single agent or
combination with ipilimumab
• NSCLC – metastatic; with progression on or after platinum-based
chemotherapy and EGFR or ALK therapy if EGFR or ALK positive
• Renal Cell – advanced disease who have received 1 or 2 prior
therapies
 Summary – ORR in patients with advanced NSCLC, melanoma,
renal cell carcinoma
•
•
•
•
•
65 of 306 patients had ORR (CR or PR)
30 of those 65 (46%) had response evident at first tumor eval (8wks)
42 of those 65 (65%) had response lasting >1yr
35 of those 65 (54%) had response ongoing at time of data analysis
Response persisted off the drug
Nivolumab pkg insert www.opdivo.com, Atkins MB et al. Clinical Care Options slideset 2014.
Immunotherapy: PD-1 inhibitors
 Nivolumab in Hodgkin’s Lymphoma
• Phase I – 23 patients who failed >3 previous regimens
including brentuximab vedotin and HSCT
• ORR 87% (20/23 patients) w/ CR in 4 (17%) with 40-wk
follow-up
• No life threatening toxicities or treatment deaths
 Activity in breast, ovarian, colon, bladder, hepatic, gastric,
head & neck, pancreatic, GBM, lymphomas, & many others
 Multiple combinations being studied (ie: with vaccines &
with other targeted drugs)
Nivolumab package insert www.opdivo.com, Mulcahy N. Medscape.2014. Abstr 289 & 290.
Immunotherapy: PD-1 inhibitors
 Pembrolizumab (Keytruda®) – FDA approval
• Melanoma – unresectable or metastatic
• NSCLC – metastatic; with progression on or after
platinum-based chemotherapy and EGFR or ALK therapy
if EGFR or ALK positive
• Activity in SCLC, esophageal, breast, ovarian, head &
neck, pancreatic, lymphomas, & many others
 Former President Jimmy Carter
• Melanoma diagnosed August 2015 – liver & brain mets
• Surgery, radiation, pembrolizumab
• Currently no evidence of disease including brain mets
Pembrolizumab pkg insert www.keytruda.com, Mulcahy N. Medscape.2014. Abstr 289 & 290, Mills D 2015
www.healthline.com
Immunotherapy: PD-1 inhibitors
 Disease can get worse before it gets better
 Four distinct response patterns associated with favorable
overall survival (OS)
• Response in baseline lesions
• Stable disease with slow decline in tumor volume
• Response following an initial increase in tumor volume
• Response following appearance of new lesions
 Infiltration of patient immune cells can cause an initial
increase in tumor volume or appearance of new lesions on
imaging scans (know as pseudoprogression)
 Need 8-12 doses to accurately evaluate patient response
Atkins MB et al. Clinical Care Options slideset 2014.
Immunotherapy: PD-1 inhibitors
 Immune-mediated toxicity
• Overall, gentler than CTLA-4 inhibitors
• Occasional (5-20%)
• Fatigue
• Rash – maculopapular, pruritis
• Diarrhea/colitis – initiate steroids early, taper slowly
• Hepatitis/liver enzyme abnormalities
• Infusion reactions
• Endocrinopathies – thyroid, adrenal, hypophysitis
• Infrequent (<5%)
• Pneumonitis
• Grade 3 or 4 toxicities are uncommon
Atkins MB et al. Clinical Care Options slideset 2014
CAR-T Therapy
 Chimeric antigen receptor (CAR) T cell therapy
 T cells are transduced with tumor specific CAR
 Process – blood drawn from patient
• T cells extracted using leukapheresis
• Transduction of T cells with retroviral vector
encoding CARs
• CAR-T cells reintroduced into patient – two daily
infusions
• “Warrior” T cells seek out & destroy enemy cancer
cells
Purwar R. Engineered T cells slideset 2016., Park JH. Conference Correspondent.ASH 2015 abstract 682.
CAR-T Therapy
 Advantages
• Fast & high response rates – 91% CR pediatric ALL; 82%
CR adult ALL
• No HLA typing needed (like with allogeneic HSCT)
• Side effects less harmful than chemo or allo HSCT
• Potential to target many antigens (protein,
carbohydrate, lipids)
• Cut cost by at least 30% compared to allo HSCT
 Challenges
• Cytokine syndrome – treat with steroids
• Heavily pretreated patients may not have enough T
cells
• Long-term sequelae & relapse rates currently
unknown
Purwar R. Engineered T cells slideset 2016., Park JH. Conference Correspondent.ASH 2015 abstract 682.
Immunovirus
 Therapeutic vaccine – different from prophylactic vaccines
 Tumors & viruses have dynamic interactions
• Malignancy can suppress normal antiviral responses
• Many viruses preferentially infect cancer cells
• Viral infection can ravage a tumor while leaving adjacent healthy
cells untouched
 Two mechanisms
• Modified virus can induce tumor cell lysis through replication
within tumor cells
• Virus can activate T cell response against tumor antigens through
dendritic cells
• Injected directly into tumors, but showing effect on cancer
elsewhere in the body
Ledford H. Nature 2015;526:622., Pietrangelo A. Heathline News 2015 www.healthline.com
Immunovirus: Talimogene
laherparepvec (Imlygic®)
 First oncolytic viral therapy approved in the U.S.
 FDA (Oct 27, 2015) – local treatment of unresectable cutaneous,
subQ, & nodal lesions in pts with melanoma recurrent after initial
surgery
 Genetically modified herpes simplex virus – replicates in tumors &
produces GM-CSF
• Causes cell lysis – releases tumor-derived antigens & GM-CSF
• Elicits further antitumor immune response
 OPTiM trial – phase III multicenter, open label, randomized
• 436 advanced melanoma patients; Imlygic® vs GM-CSF
• Extended survival by 4.4 months; time to response 4.1 months
• SE – fatigue, chills, fever, nausea, flu-like symptoms, injection site
pain, cellulitis
 Being studied in combination with PD-1 inhibitors in melanoma &
other solid tumors
Talmogene laherparepvec package insert www.imlygic.com
Immunovirus: PVS-RIPO
 PVS-RIPO – genetically engineered poliovirus against GBM
• Genetic code of rhinovirus spliced into polivirus to remove it’s
disease-causing ablility
• Safety – in primates & humans; no nerve cell damage, no ability to
cause poliomyelitis, no ability for PVS-RIPO to change back to wild
type poliovirus
 Infused directly into patient’s tumor
• Catheter placed into tumor, 2.5ml PVS-RIPO infused in the ICU over
6.5 hours, catheter removed, patient followed, no further treatment
 Kills tumor cells & recruits immune response vs. the tumor
 SE – fever, flu-like, diarrhea, headache, N/V, limb weakness, breathing
difficulties, brain swelling, etc
 Future – phase II/III in adults, pediatric brain tumors, other tumor types
(showing response in lung, breast, colon, liver, pancreas, kidney, etc)
Gromeier M, et al. 2016 www.cancer.duke.edu
Immunovirus: What’s Next
 Other promising virus therapies
• Breast cancer vaccine – targets HER-2 neu receptor
• CimaVax-EGF – lung cancer vaccine developed in Cuba
• Respiratory enteric orphan virus (Reolysin®)
• Ovarian cancer vaccine (>80% of patients have metastatic disease)
• Trials ongoing in lung, colon, melanoma, sarcoma, head & neck
 Room for improvement
• Need a way to deliver the vaccine systemically
• Requires a technique to prevent an immune attack to the virus
prematurely
 Many viruses being studied
• Vesicular stomatitis virus that infects cattle but not humans
• Virus that hitch-hikes on certain blood cells camouflaged from immune
system
Cohn D. Innovations in Science 2015. www.standup2cancer.org
Chen DS, et al. Immunity. 2013;39:1-10.
Immunotherapy for the Future
 BiTE Anitbodies
• Bridges a target antigen on surface of cancer cell to CD3+ on the
cytotoxic T lymphocyte
• Engages T cell, bypassing MHC Ag-dependent activation of T cell
• T cells release proteolytic enzymes that lyse the tumor cell
• BiTE Ab then moves through bloodstream targeting other cells
• Activated T cells remain active
 Universal cancer biomarker???
• DNA methylation mark around ZNF 154 found in 15 tumor types
in 13 different organs
• Tumors often shed DNA into bloodstream
• Advantage – no prior knowledge of the cancer required
• Could be used to diagnose cancer earlier, monitor during
treatment, or identify high risk patients
BiTE antibodies www.amgenoncology.com, News release NIH 2016 Feb www.nih.gov
Currin R. CurrinBIOTECH Newsletter. 2011;1(10)
Immunotherapy for the Future
 TMEM (tumor microenvironment of metastasis)
•
•
•
•
Research has uncovered how breast cancer spreads
TMEM - 3 specific cells coming together
Tumors with high TMEM score are more likely to spread
New drug target – could lead to treatments to stop cancer from
spreading
 Magic wands
• Hand held probe connected to a laser that shines light onto
human tissue
• Can distinguish cancer cells from normal cells
• Neurosurgeons testing on brain tumor patients during surgery
• Trials showing the probe detects cancer cells when they are there
95/100 times
Pietrangelo A. Heathline News 2015 www.healthline.com, UC Davis Comprehensive Cancer Center 2016 www.ucdavis.edu
Immunotherapy for the Future
 IDH2 Inhibitors
• IDH2 mutations have been identified in many solid tumors &
hematologic malignancies
• 15% of AML patients – unlikely to respond to other treatments;
majority in the study had relapsed or refractory disease
• IDH2 inhibitor (AG-221) – pill taken daily for AML ; ORR 56% (24 of 45
patients) with 15 CRs
• Allows AML cells to develop into healthy neutrophils
• SE – mostly disease-related rather than treatment-related
 Proteomics
• Assessing proteins in the blood for cancer screening
• Research ongoing in ovarian cancer, oral cancers, & lung cancer
 Intraoperative radiation
• Single shot of radiation during surgery
• Less SE & improved outcomes
Mulcahy N. Medscape 2014 www.medscape.com, Crane K. US News 2014 www.health.usnews.com
Immunotherapy for the Future
 CRISPR technology
• Clustered regularly interspaced short palindromic repeats
• Gene editing technique used to inactivate genes & see what happens
• Can reveal which human genes are essential & which matter
specifically to cancer cells
• Humans have 20,000 – 25,000 genes – between 1600 & 1800 of
these are essential & less likely to carry mutations
• Essential genes in cell lines of 8 different cancers have been
catalogued so far
• Goal – find genes that are expendable in healthy cells but crucial in
tumors
• Not yet sure if we will find enough genes that differentiate cancer
cells or if they will be targetable
• Project Achilles – initiative that will use CRISPR to search for specific
weaknesses in over 500 cancer cell lines
Yong E. The Atlantic Nov 2015 www.theatlantic.com, CBS News Nov 2015 www.cbsnews.com
Patient Case #1: PD-1 Inhibitor
 ED 33yo male with Hodgkins Lymphoma
 Apr 2011: standard chemo w/ ABVD (doxorubicin,
bleomycin, vinblastine, dacarbazine) x6 cycles
 2nd line chemo: GDP (gemcitabine, dexamethasone,
cisplatin)
 2012: autologous stem cell transplant → recurrence
 Salvage chemo: brentuximab vedotin (Adcetris®)
 Salvage chemo: GDP, MOPP (mechlorethamine,
vincristine, procarbazine, prednisone), bendamustine
 Dec 2014: allogeneic stem cell transplant → recurrence
 Aug 2015: nivolumab → almost no evidence of disease
Patient Case #2: CAR-T Therapy
 JA 3yo male with Acute Lymphocytic Leukemia (ALL)
 2013 – diagnosed at age 18 months
 2 year battle chemotherapy → relapsed twice
 Allogeneic stem cell transplant → relapse
 Out of treatment options other than hospice
 CAR-T Therapy → no evidence of disease x 9 months
Strongagainstcancer.org
Patient Case #3: Immunovirus
 SL 20yo female with tennis ball sized GBM
(glioblastoma multiforme) brain tumor
 2011 – surgery; 98% removed
 Radiation & chemotherapy (temozolamide)
 Recurrence 2012 → 1st patient on Phase I Polio
immunovirus trial at Duke University
 Treatment began in May → tumor is larger by June
 No evidence of tumor x3 years
60 Minutes: Killing Cancer Part 1 & 2, Mar 29, 2015. Available at www.cbsnews.com
Assessment Question #1
 The most prevalent immune cells targeted by
monoclonal antibodies to kill cancer cells are:
a) Plasma cells
b) T cells
c) Dendritic cells
d) B cells
Assessment Question #2
 Which of the following is a disadvantage of CAR-T
therapy
a) It is 30% more expensive than an allogeneic stem
cell transplant
b) HLA typing is needed before treatment can begin
c) There are more side effects than with traditional
chemotherapy
d) We don’t know the long-term effects or
curability of CAR-T therapy
Assessment Question #3
 Which of the following is a disadvantage of using
viruses to kill cancer cells?
a) The virus may cause a viral infection in the
patient
b) Immunoviruses cannot be used if the patient
has received prior chemotherapy
c) The virus may not reach all tumor cells if the
tumor has spread throughout the body
d) Healthy cells surrounding the virus-infected
tumor cells become damaged by the virus
Conclusions
 Cancer will soon be the #1 cause of death in the United States
 Cancer treatment is entering a new era – stimulating the
patient’s own immune system to fight cancer
 Immune checkpoint inhibitors have demonstrated success in
treating cancer patients with advanced disease
 CAR-T therapy is an exciting new way to target the immune
system & may eventually replace allogeneic HSCT
 Immunoviruses are being used in innovative ways to treat
cancer with some promising long-term results
 Technology will change how cancer is prevented, detected,
and treated in amazing new ways
 Today’s patient cases illustrate how technology & innovations
are providing new hope for cancer patients & their loved ones
References
 United States Cancer Statistics (1999-2012). Available at:
www.cdc.gov/uscs
 Help find a cure for childhood cancer. Available at:
www.strongagainstcancer.org/science
 Sweeney N, et al. The value of innovation in oncology: recognizing
emerging benefits over time. Boston Healthcare. May 2015
 Goodman B et al. History of cancer timeline. Based on the book: The
Emperor of All Maladies by Siddhartha Mukherjee. Available at:
www.cancerfilms.org
 The History of Cancer. Available at: www.cancer.org
 Mills D. Researchers applaud President Obama’s plan for
“moonshot” against cancer. Available at: www.healthline.com. Jan
13, 2016.
 Dendreon Corporation. Cancer immunotherapy: fundamental
concepts and emerging role. 2013. Available at:
www.dendreon.com
 BiTE Antibodies: designed to bridge T cells to cancer cells. 2015.
Available at: www.amgenoncology.com.
References
 Pelly S. 60 Minutes: Killing Cancer Part 1 & 2. Mar 29, 2015.
Available at www.cbsnews.com
 Atkins MB et al. Immunotherapy in cancer: from principles to
practice. Clinical Care Options slideset 2014.
 Bristol-Myers Squibb. Nivolumab package insert (revised 1/2016).
Available at www.opdivo.com
 Merk. Pembrolizumab package insert (revised 12/2015). Available at
www.keytruda.com
 Mulcahy N. PD-1 blockade arrives in hematologic cancer. American
Society of Hematology 56th annual meeting, Dec 2014. Abstr 6125.
Available at: www.medscape.com
 Mills D. Drug used in Jimmy Carter’s cancer treatment among a new
generation of immune therapies. 2015 Dec. Available at
www.healthline.com
References
 Purwar R. Engineered T cells: next generation cancer immunotherapy.
Slideset 2016.
 Park JH. CAR-modified T-Cells in adult patients with
relapsed/refractory B cell ALL. Conference Correspondent. 2015 ASH
Abstr 682.
 Ledford H. Cancer-fighting viruses near market. Nature.
2015;526:622-23.
 Pietrangelo A. Immune systems now a major focus of cancer
treatment research. Healthline News 2015. Available at:
www.healthline.com
 Gromeier M, et al. Targeting cancer with genetically engineered
poliovirus (PVS-RIPO). 2016. Available at: www.cancer.duke.edu
 Cohn D. Virus Therapy. Innovations in Science 2015. Available at
www.standup2cancer.org
 News release. NIH researchers identify striking genomic signature
shared by five types of cancer. 2016 Feb. Available at: www.nih.gov
References
 Pietrangelo A. Researchers find “doorway” that allows breast
cancer to enter the bloodstream. Healthline News 2015.
Available at: www.healthline.com
 UC Davis Comprehensive Cancer Center. Magic wands and other
innovations to find cancer. 2016. Available at: www.ucdmc.edu
 Mulcahy N. No chemo: agent represents a new way of thinking
about AML. Medscape 2014. Available at: www.medscape.com
 Crane K. 7 Innovations in cancer therapy. US News 2014.
Available at: www.health.usnews.com
 Yong E. The new gene-editing technique that reveals cancer’s
weaknesses. The Atlantic 2015 Nov. Available at:
www.theatlantic.com
 CBS News. Could revolutionary gene-editing technology end
cancer? 2015 Nov. Available at: www.cbsnews.com
Questions
[email protected]