Microfluidic assay to predict patient-specific multiple myeloma clinical response

DESCRIPTION provided by applicant Multiple myeloma MM is a debilitating and currently incurable hematological malignancy While the median survival has increased to years MM patients ultimately relapse and become resistant to therapy Once they reach this stage it is often a trial and error process until an effective therapy can be found Furthermore the MM bone marrow tumor microenvironment plays a significant role in disease progression and resistance to therapy There is a critical need for a clinical tool able to predict therapeutic response to drugs for specific patients We have developed an ex vivo microfluidic platform MicroC tm that can rapidly analyze the therapeutic response of a patientandapos s MM cells to various drugs in coculture with their own microenvironmental cell components When MicroC tm was initially tested by measuring the ex vivo toxicity responses of patient MM cells to bortezomib a drug commonly used in MM therapy MicroC responses could be segregated into two groups which retrospectively correctly identified all patients as either clinically responsive or non responsive to bortezomib containing therapies We propose to develop MicroC as a companion diagnostic CD for bortezomib and other MM therapies To achieve this project Lynx Biosciences is uniquely positioned through three key collaborations Dr Natalie Callander as a collaborator and Director of the University of Wisconsin Myeloma Clinical Program Professor David Beebe as an expert consultant and pioneer of simple microfluidic devices and the Morgridge Institutes for Research enabling Lynx to have direct access to prototyping facilities and experts in device design for manufacturability The proposal consists of two aims Standardize bonding and fabrication of the MicroC device by changing the material it is currently fabricated of to polystyrene PS in order to accommodate testing of all drugs and facilitate high throughput fabrication Initiate a small clinical trial of patientswho will be receiving bortezomib containing therapies as standard of care and comparing their clinical responses to ex vivo MicroC responses to bortezomib Using the same samples from these patients we will also assess ex vivo responses to cyclophosphamide and lenalidomide two drugs commonly used in combination with bortezomib to determine the optimal dose at which to segregate their ex vivo responses At the conclusion of Phase I the sensitivity specificity of MicroC as a proof of concept CD for bortezomib will have been determined This will allow us to calculate the sample size of a prospective clinical trial in Phas II to test the predictive capabilities of MicroC by using the PS devices to segregate patients for therapy containing bortezomib and potentially other therapies Ultimately MicroC may be applied for use in reviving drugs which were not successful in late stage clinical trials identifyng potentially successful preclinical drugs prior to initiation of clinical trials and hematological malignancies other than MM PUBLIC HEALTH RELEVANCE Currently many cancer patients including multiple myeloma MM patients are treated empirically or with drug combinations based on their physicianandapos s experience and clinical trial data it is impossible to predict which cancer therapies will be successful for individual patients Cancer therapies including MM therapies are also very costly andgt $ per month with potentially significant side effects In this proposal we aim to develop an assay technology which enables clinicians to make more informed decisions regarding therapy course utilize precious time more effectively and reduce the cost associated with ineffective therapies