• Formulation development and CMC studies
• Assistance in designing preclinical and clinical pharmacology studies
  • PK
  • PD (efficacy and toxicity)
  • Biomarkers
• Coordination of studies with Animal Studies Core
• Analysis and interpretation of data
• Generation of reports and publications

Individual interview days will be scheduled at times convenient for applicants and institutions. Each applicant and program will communicate to identify the ideal time to conduct the interview. Our hope is to have all of the interviews for an applicant in one consecutive period.

Measurement of drugs in biological matrices or from solution using an LC-MS/MS or ICP-MS-based assay

Three tiers of sample analysis offered based on complexity:

• Tier 1: Relative quantitation, or absolute quantitation using a non-validated assay (data adequate for preliminary data for grant proposal)
• Tier 2: Absolute quantitation of a small molecule drug , dosed as a small molecule or nanoparticle formulation using a validated assay
• Tier 3: Absolute quantitation of a complex drug or carrier-mediated agent such as a monoclonal antibody, drug conjugate or polymer

*Costs begin at $61 per sample.  Please contact Allison Schorzman for pricing.

*The sponsor is responsible for providing the reference material and internal standard.

Sample matrices:

• Whole blood
• Plasma
• Serum
• Tumor
• Tissue (liver, spleen, brain, kidney, pancreas, heart, etc.)
• PBMCs
• Red blood cells
• Cerebral spinal fluid
• Saliva
• Urine
• Feces

**Note: Assays for other drugs, analytes and substances can be developed and validated as needed.

LC-MS/MS and ICP-MS assays can be developed for a variety of biological matrices such as plasma, tissues and tumor. Standard techniques include protein precipitation, liquid-liquid extraction, solid-phase extraction, but the assay can be tailored to meet needs of analyte and the study. The method development follows FDA guidelines for biological method validation. The ATPAC is able to perform a partial cross validation of an assay reported in the literature.

Three tiers of sample analysis offered based on complexity:

• Tier 1: Test the ability to extract a drug from a biological matrix; optimize LC and MS parameters; to measure presence of drug or relative quantitation
• Tier 2: Includes Tier 1 assay development components; includes validation with three days of accuracy and precision, includes necessary stability studies for a small molecule drug; includes small molecules from a solvent-soluble nanoparticle; multiple drugs can be included in the same assay.
• Tier 3: Includes Tier 1 assay development components; includes validation with three days of accuracy and precision, includes necessary stability studies for a complex drug or carrier-mediated agent (monoclonal antibody, conjugate drug, polymer).
  • The ATPAC has novel sample processing and analytical methods for the following agents and forms:
    • Nanoparticles, CMA and ADC = encapsulated/conjugated and released drug, parts of the carrier (e.g. polymers and PEG) and ligands.
  • Biologics (e.g. proteins)
  • Monoclonal antibodies
  • Polymers (e.g. PEG)
  • Intracellular exposures

*Costs begin at $920 per assay. Please contact Allison Schorzman for pricing.

*The sponsor is responsible for providing the reference material and internal standard.

Interactions between the immune system and anti-cancer agents have a critical influence on their pharmacologic disposition and thus contribute to the variation in efficacy and toxicities observed. A major objective is the correlation of immune cell functional characteristics with study-related outcomes.

Biomarkers of Immune Cell Function

The ATPAC Lab offers assays that evaluate the functional activity of cells of the innate immune system. These markers have been utilized and linked to various processes that can affect the pharmacologic disposition of advanced formulations (e.g. nanoparticles, therapeutic monoclonal antibodies, antibody-drug conjugates, etc.).

• PhenoGLO: An ex vivo flow cytometry–based, high-throughput screening platform (HTSP) to measure the phagocytic function and reactive oxygen species (ROS) production by phagocytic immune cells to evaluate the bidirectional interaction between these cells and nanoparticles, conjugates, and antibody–drug conjugates. Importantly, this method also predicts nanoparticle pharmacokinetics and pharmacodynamics in humans where the MPS system seems to drive the clearance, efficacy, and toxicity of nanoparticle agents.

Immune Cell Signatures

The phenotype of immune cells can be determined by labelling cells with panels of fluorophore-conjugated monoclonal antibodies followed by subsequent analysis by flow cytometry. Panel compositions are subject to change without notice.  Representative validated panels are listed below but can be customized by consulting ATPAC staff.

• Fc-gamma Receptors [FcγRs]: FcγRs bind to the IgG molecule through its Fc portion. These are expressed in differing combinations at the surface membrane of the various immune cells. However, binding and internalization by circulating phagocytes serves as a unique mechanism of elimination/clearance for therapeutic antibodies and antibody-drug conjugates, increasing the inter-patient variability of these agents depending on patient-specific phenotypes.
• Toll-like Receptors [TLRs]: TLRs play a vital role in innate immunity and are expressed on a variety of cell types. These proteins are known as pattern recognition receptors and help detect bacteria, fungi, protozoa, and viruses. TLR activation leads to a wide range of effects, including inflammation, complement activation, and phagocytosis.

Cytokines/Chemokines

The ATPAC Lab offers enzyme linked immuno-assays (ELISA) for analyses of human or murine fluid samples (serum/plasma, tissue homogenate).

Contact us directly for inquiries regarding custom panels or modifying current panels to include additional markers of interest.

• PK parameter calculations
• PK/PD analyses and interpretation
• Generation of reports and publications

• Summary of measured concentrations
• Summary of analytical methods used to generate data (suitable for publication)
• Summary report with figures and text, as needed

• Thermo TSQ Quantum Ultra triple quadrupole mass spectrometers with Shimadzu LC-20AD series HPLC
• Thermo LTQ Orbitrap Discovery mass spectrometer with Shimadzu LC-20AD series HPLC
• Agilent 7700 inductively-coupled plasma mass spectrometer (ICP-MS)
• Shimadzu 20 series HPLC with fluorescence detection

• Complete ATPAC Request for Service form
• Contact Bill Zamboni (Lab Director) or Robert St. Claire (Director of Operations) to discuss details regarding the research study. Contact Gail Moriarty if you would like to schedule a meeting.