Late-Breaking Abstracts
2010 Annual Meeting; Washington, D.C., October 2-4, 2010 3
International Society for Biological Therapy of Cancer (iSBTc; now known as the Society for Immunotherapy of Cancer; SITC)
-162-
USING TIMING TO SYNCHRONISE IMMUNOTHERAPY THROUGH
MICROMANIPULATION OF THE UNDERLYING TUMOR IMMUNE RESPONSE:
FROM COLEY TO ROSENBERG, LOTZE, ALLISON, WOLCHOK AND BEYOND!
Brendon J. Coventry1, Martin L. Ashdown2, Svetomir N. Markovic3
1Surgery and Immunology, University of Adelaide, Adelaide, SA, Australia
2Medicine, University of Melbourne, Melbourne, VIC, Australia
3Medical Oncology, Mayo Clinic, Rochester, MN
Introduction: Immunotherapy studies in advanced cancers appear to show that the immune
response can be driven in either an ‘effector’ or ‘regulatory’ direction or a ‘mixture’ of these,
leading to the heterogeneous clinical responses (CR, PR, PD) seen. Using CRP as a marker, we
have shown that a repeating cyclical, dependent, sequential, orchestrated, homeostatic
physiologic process appears to be occurring in most, if not all, cancer patients, most likely as a
result of chronic antigenic stimulation. The correct timing of immunotherapy or chemotherapy
with this ‘immune cycle’ appears to be associated with better cancer control and improved
clinical outcomes.
We are concerned that the timing of therapy with respect to the underlying tumor immune
response fluctuations is the principal determinant of efficacy in cancer treatment. The
observations and model may also extend to other chronic inflammatory states to determine
therapeutic efficacy.
Methods: Using serial CRP measurements in late-stage cancer patients, we have recently been
able to expose sequential and time dependent oscillations in the inflammatory/ immune response
that may represent a homeostatic, repeating or cyclical process of tumour immune
responsiveness then tolerance. The periodicity of these cycles appears to be reproducible at
approximately 6-7 days.
By serially measuring CRP around the time of vaccination or chemotherapy, the position on the
underlying immune curve can be established. Timing with respect to this cycle appears to be
critical to modulating the immune system with each intervention, and pivotal to the clinical
efficacy of therapy (1,2).
Results: Using these methods, we have been able to correlate the timing of vaccination/
chemotherapy with the induction of clinical responses. Induction of complete responses, stable
disease, slowed growth even with persistent metastatic disease, appears possible using these
principles, thereby improving overall survival.
Conclusions: The historical ‘random successes’ seen with vaccines, cytokines and receptor
directed monoclonal antibodies may be due to their fortuitous accidental interference with the
underlying persistent, homeostatically regulated tumor immune kinetics by their ‘random’
untimed administration. By accurately and appropriately synchronizing therapy to each patient’s
immune system’s periodic oscillations - immune cycle - we predict that the current low random
immunotherapy successes seen to date, can be made more predictable by accurately timing
therapy better, and will achieve greater clinical efficacy.
Where have you heard the key to an immune response is dose and timming.
Right Here
Melanoma and the Magic Bullet
The Research paper called
Melanoma and the Magic Bullet
The Research paper called
The Making of an Immune Response by Combinatorial Therapy Using Anti-CTLA-4 Blockade and Interleukin-2 “It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”
~Charles Darwin~
Take Care,
Jimmy B