IMPACT²: Immune Effector Engineering and Screening

IMPACT² (the IMmunotherapy Platform for Antibody, mRNA and CAR Therapeutics and Translation) supports “hit-to-lead” screening and development of antibody-based drug candidates. Through institutional support and a Research Infrastructure Grant from the Massachusetts Life Sciences Center (MLSC), IMPACT² has assembled a unique suite of tools for the high-throughput characterization of antibody-based immunotherapies, enabling investigators to engineer identified antibody “hits” into libraries of therapeutic antibody-based immune effector formats and to support functional characterization.

Library-Based Screening to Identify Therapeutic Leads

Our workflow begins by engineering antibody discovery-derived outputs of 10³ to 10⁴ antibodies into libraries of immune effectors that are assayed via broad pooled screening strategies to identify several hundred candidates. These candidates can be further screened via targeted arrayed screens to identify one or two lead candidates for pre-IND assessment.

Our screening services are compatible with antibodies discovered through both in vitro and in vivo strategies. We partner closely with therapeutic project PIs to develop custom in vitro strategies that best accelerate the identification of clinically relevant, final format therapies.

Equipment and Technology

IMPACT² maintains specialized automation, screening, and characterization tools to support platform workflows (also utilized by LAUNCHPAD). Learn more about the instrumentation that supports our workflows.

Explore Our Equipment

Workflow and Services

Pooled Screens
To Assess Antibody Discovery Outputs in Final Format

HT Arrayed In Vitro Screens
To Assess Candidate
Functionality

Deep Profiling of
Leads / IND-Enabling Studies

IND-Ready Drug Candidate
CAR Effector or Biologic

Pooled Screening Workflows

Our team uses high-throughput, pooled screens using engineered cell lines to generate isogenic, stable CAR-expressing Jurkat T cell libraries. Pooled screens can accommodate large diversities (>10,000 clonal members) to assess basic functional readouts of activation and tonic activity.

Arrayed Workflows & Functional Screens

High-throughput, Arrayed Screens of Cell Therapy and Biologics Candidates

For those cell therapy or antibody candidates displaying strong, target-specific activation in pooled screens, more comprehensive functional screening can be performed in a high-throughput arrayed format using primary, donor-derived immune effector cells. In these screens, each drug candidate can be individually assessed for cytotoxicity at varying concentrations or effector-to-target ratios, tonic signaling or target-independent signaling, epitope targeting via domain mapping or epitope binning, and persistence and proliferation in response to repeated stimulation with target-expressing cells (i.e., repeat antigen-based proliferation).

High Resolution Screens of Lead Candidates

Our arrayed screens of <10 lead cell therapy or biologics candidates identified via HT screens replicate a similar panel of assays at a greater resolution (i.e., larger range of E:Ts, etc.). Our team can help identify a small panel of 2 to 3 leads that can be advanced for in vivo validation by our partnering investigators.

Support for IND-enabling Studies

While our primary focus is on helping investigators screen immunotherapy libraries, IMPACT² can also help support and coordinate IND-enabling studies on an optimized candidate including off-target specificity, CRS potential and on-target/off-tumor toxicities.

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Need Binders First?

If your program needs target-specific binders before engineering and screening, LAUNCHPAD can generate fully human antibody hits using display-based discovery workflows.

Explore LAUNCHPAD

Interested in collaborating?

Complete our brief project interest form to share your project background, goals, target, and services of interest.

Project Interest Form

Working with IMPACT²

Our engagements are collaborative and often iterative — optimizing a lead immune effector or biologics candidate can involve several rounds of engineering: binders or other structural elements are identified, combinatorically screened for function, and subsequently engineered to ensure the desired specificity and sensitivity to one or multiple targets.

We welcome collaborations with principal investigators with expertise in disease biology and drug development, both within and beyond Dana-Farber Cancer Institute. If you'd like to learn more about our workflows and how we might collaborate, please reach out.