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CVM-Pharmacy Spring SymposiumCVM-Pharmacy Spring SymposiumWhat CVM has to Offer (Oncology) What CVM has to Offer (Oncology)
(ACCR)(ACCR)
Jaime F. ModianoJaime F. Modiano
The Animal Cancer Care and Research Program (ACCR)
• Joint program of CVM and MCC
• Basic, translational, and clinical research mission
• Educational and training mission
• Clinical service delivery mission
Onc Section Faculty and Research Interests
• Jaime Modiano – Professor– Cancer biology, immunology, genetics
• Mike Henson – Associate Professor– Translational therapy
• Fekadu Kassie – Assistant Professor– Cancer chemoprevention
• Erin Dickerson – Assistant Professor– Drug targeting and cancer metabolism
• Antonella Borgatti – Assistant Professor– Translational therapy
• Daisuke Ito – Assistant Professor (6/1/13)– Lymphoma biology
• Claire Cannon – Research Associate (Onc Fellow)– Translational therapy
Other ACCR Faculty
• Liz Pluhar and Vicki Wilke (CVM, Surgery)• Subree Subramanian (SOM - Surgery)• Aaron Sarver (MCC)• David Largaespada (MCDBG)• Khalil Ahmed (VA and SOM, LMP)• Jeff Miller (SOM, Medicine)• Dan Vallera (SOM, Radiology)• Many others
Research Opportunities
• > 1 million dogs are diagnosed and managed with cancer in the U.S. each year
• Intact immune system• Compressed life span• Cancers are influenced by similar factors (e.g. age,
nutrition, gender, reproductive state, environmental exposure) www.canusgoatsmilk.com
Key Programs• Brain cancer (Pluhar, Moertel)
• Sarcomas (Borgatti, Weigel, Largaespada, Spector, Wilke, Sarver, Subramanian, Modiano, Dickerson, Clohisy, et. al.)
• Hematologic malignancies (Ito, Miller, Modiano, O’Brien, Linden, Bachanova, Burns)
• Chemical carcinogenesis and prevention (Kassie)
• Etiology and cancer genetics (Modiano, Sarver, Subramanian, Largaespada, O’Brien, Kassie)
• Therapeutic targeting and microRNAs (Subramanian, Dickerson, Vallera, Ahmed, Kassie)
• Clinical trials (Borgatti, Henson, Cannon)
Resources• Tissue bank
– >100 cell lines (mostly sarcomas) and >1200 tumor samples with blood for germ line DNA (e.g., T:N sequencing) with broad geographic distribution
– Bank was developed as a joint effort with collaborators at Broad and NCSU, and supplemented from local patient samples and from U of M clinical studies
Clinical Opportunities
• Studies originating locally (home grown therapies)
• Studies originating from contracts or collaborations (imported technology)
• Hypothesis testing and hypothesis generating
Tumor Distribution at the CVMAll Admissions
Tumor Distribution at the CVMNew Diagnoses
- New Diagnoses
Clinical Oncology Studies at the CVMLymphoma
(LSA)
Karyo-1 CRM1 inhibitor
Safety, dose-finding study
Dogs with lymphoma, otherwise healthy
Fully funded Borgatti C
LSA Karyo-2 CRM1 inhibitor
Efficacy study
Dogs with naïve and first relapsed lymphoma, otherwise healthy
Fully funded Borgatti A
LSA MADGIC Sample collection study
Discovery and characterization of heritable and somatic cancer mutations in Golden Retrievers
Dogs with lymphoma Biopsy samples and blood samples
Modiano A
LSA LICKing Lymphoma
PSC-833
Ablation of tumor initiating cells, safety and efficacy study with concurrent doxorubicin chemotherapy
Dogs with lymphoma, otherwise healthy
Study drug
$2,000 to owners towards chemotherapy
Modiano C
LSA Idarubicin Prospective, open- label, phase I
Dogs with measurable lymphoma
Study costs Husbands C
LSA Acupuncture Efficacy of acupuncture in alleviating chemotherapy-induced side effects
Concurrent doxorubicin chemotherapy
Randomized, double-blinded
Dogs with lymphoma Covers the cost of acupuncture
Choi P
Disease Study Description Inclusion/exclusion Incentive PI Status
Brain tumors
(Glioma,
Meningioma)
1) Gene therapy + immunotherapy vs. immunotherapy alone
2) Gene therapy + chemotherapy
3) Immunotherapy + chemotherapy
Study selected based on diagnosis
MRI prior to enrollment
No evidence of systemic disease
Fully funded Pluhar A
Any histology,
*histiocytic sarcoma
Compassionate use of TTG100 in canine spontaneous cancer
Safety and efficacy of TTG100
ECG, PK series, Visits Day 1, 22, 43, 71, 99
Any measurable disease
SOC not successful or declined
No anticancer therapy for at least 3 weeks prior to enrollment
Drug and PK levels covered
$1,000 credit + $1,000 credit to owners of Bernese Mountain Dogs (from breed club)
Henson A
Various histologies
*liver cancer
Microwave ablation + immunotherapy
Safety and efficacy of ultrasound-guided microwave ablation combined with adjuvant
Dogs and cats with unresectable masses amenable to microwave ablation
Partially-funded Ober A
Any histology, including breed specific cohorts
COTC016: A Pilot Study Assess feasibility of tissue collections and molecular profiling for future comparative oncology personalized medicine
Any measurable disease
$1,000 credit to owners + costs associated with sample collection
Henson C
Disease Study Inclusion/exclusionDescription Incentive PI
Clinical Oncology Studies at the CVMStatus
Clinical Oncology Studies at the CVMHemangiosarcoma (HSA)
1) SRCBST
Bispecific ligand targeted toxin
2) MADGIC
Dose-finding
Splenectomy and doxorubicin chemotherapy
PET-CT at baseline and on day 21 if abnormalities on the initial scan
PK samples
Sample collection
Splenic HSA
No evidence of metastasis
Enrollment post splenectomy
All dogs with HSA
Study rechecks are covered + $3,300 towards SOC chemotherapy
Samples/pathology
Modiano A
Borgatti
Vallera
Modiano A
Osteosarcoma
(OS)
1) OSAL (Salmonella-IL2)
2) miR31
Safety and efficacy
Concurrent doxorubicin chemotherapy
Markers of pulmonary metastatic disease
Naïve appendicular OS
Naïve appendicular OS
$2,000 incentive
Pays sample collection
Wilke A
Kassie A
Fritz
OS Palladia/Piroxicam/Cyclophosphamide maintenance therapy
Impact and efficacy of maintenance therapy following amputation and carboplatin
Microscopic, non-metastatic OS
Partially-funded Borgatti C
Feline oral squamous cell carcinoma (SCC)
Protein kinase CK2 (nanocapsules)
Safety and efficacy Oral SCC, regional metastasis permitted, no distant metastasis or systemic disease
Treatment, rechecks, up to $2,500 towards adverse events
Cannon A
Disease Study Description Inclusion/exclusion Incentive PI Status
Clinical Investigation Center (CIC)
What Else Sets the UMN Apart?A Few Select Examples:• Translation of brain cancer therapy from dogs to humans
– “Successful Cancer Trial In Dogs Helping To Save Teenager”• Prediction and prognosis for bone cancer patients
– “U of M researchers look to dogs to better understand intricacies of bone cancer”
• Translation of cancer therapies from humans to dogs and back– Sal-IL-2 for bone cancer– Minnelide™ for bone cancer– “LICKing Lymphoma” – Novartis partnership targeting tumor
initiating cells– Bispecific Ligand Targeted Toxin for hemangiosarcoma– Gene therapy for liver tumors
What Have We Accomplished?
• Research success has allowed us to establish a level of credibility in the scientific community and created a stable partnership between CVM and MCC
• Success stories extend from the laboratory to the clinic – advancing translation