Adoptive T Cell Therapy for Malignancies in Dogs—A Model of Hope Edmund Sullivan, DVMBellingham, WA

Conflict of Interest Disclosures Edmund Sullivan, DVM

Affiliations:Fred Hutchinson Cancer Research CenterHematologics CorporationEngene OncologyThe Perseus FoundationThe NorthWest Veterinary Blood BankAdvanced Veterinary Service, Inc.Cellphire, Inc.

Dogs are the model for transplantation techniques• Demonstrated and expanded upon at Fred Hutch by Thomas, Storb, Applebaum and others

• Wide variation in phenotype is the result of a small difference in genotype

• Share environment with humans—diet, home, yard, car, and most recently identified, biome

• Life-time outcome of treatment known in brief time

Are Dogs the model for Adoptive Immunotherapy?• Selection, expansion, stimulation, and infusion of CD8+ T Cells

• Anti tumor whole-cell vaccines prior to cell harvest

• Mobilization and apheresis—enhances numbers and quality(?) of T cells

• Pilot study with dogs using T cells after CHOP chemotherapy—no consolidation

”Comet”

• 6 Yr Golden Retreiver

• T cell lymphoma—treated with an allogeneic stem cell transplant

• Secondary Malignancy—Fibrosarcoma of distal tibia

• Treated with Adoptive T Cells from allogeneic donor after the donor was primed with a whole cell tumor vaccine made from the fibrosarcoma

”Tucker”

• 5 yr Visla with B cell lymphoma that was non- responsive to induction chemotherapy

• Allogeneic stem cell transplant from brother induced a brief remission

• Adoptive T cell transfer (selected, expanded, stimulated) from the donor resulted in 4 year remission (and counting)

”Jasper”

• 9 yr Golden Retreiver with B cell lymphoma

• Autologous stem cell transplant, with subsequent relapse and disease progression

• Adoptive T cell infusions

• Molecular remission for 3 years—no evidence of lymphoma at the time of death

”Bleu”

• 9 yr Black Lab with Acute Myeloid Leukemia

• Induction chemotherapy, allogeneic stem cell transplant from niece

• Disease progression post transplant

• Allogeneic T cells—selected, expanded, stimulated—infused

• Molecular remission at time of death

”Miles Davis”, “Chad”, and “Rosco”• B Cell lymphoma

• Induction Chemotherapy

• Consolidation with high dose Cytoxan

• Molecular Remission—3 years and counting

Are Dogs a model for Adoptive Immunotherapy?

YES, they are.

• Huge area of interest in human medicine

• Few regulatory hurdles, rapid disease progression, lifetime consequences known in relatively short time

• Discoveries made in dogs will illuminate the path for people

The Path Forward

• No shortage of patients—B cell lymphoma and other malignancies are common in dogs

• Better techniques for growing the APC cells. Currently using flask-based systems

• Faster, better techniques for collecting and expanding T cells. Currently using flask-based systems which are slow (average 32 days) and susceptible to contamination

The Perseus Foundation

Our non-profit partner that is providing a research and development grant to establish adoptive immunotherapies in dogs with the hope and expectation of translation to people.