Associate Principal Scientist, TCE Discovery & Biology

Position Summary

We are seeking an experienced and highly motivated Associate Principal Scientist to join our Immuno-Oncology discovery team and contribute to the discovery and development of next-generation T-cell engager (TCE) therapeutics. This role is designed for a scientifically mature, hands-on investigator who can lead defined biology workstreams while continuing to design, execute, and troubleshoot critical experiments at the bench.

The successful candidate will bridge laboratory execution and project-level scientific leadership. They will translate program questions into integrated experimental plans, generate and interpret decision-quality data, provide technical direction to colleagues and external partners, and influence molecule optimization and progression decisions from early discovery through lead optimization and translational assessment.

The anticipated balance is approximately 40–60% laboratory work, adjusted by project phase and team needs. The role is not expected to carry the full portfolio, budget, or people-management accountability of a Principal Scientist / Associate Director, but it should operate with substantial independence and visible matrix leadership.

Key Responsibilities

1. Hands-On TCE Functional Biology

• Personally design and execute critical in vitro TCE experiments, particularly studies that resolve key molecule-selection, mechanism, or translational questions.
• Establish and optimize T-cell and tumor-cell co-culture systems using primary human T cells, PBMCs, relevant tumor cell lines, and other physiologically relevant models.
• Conduct and interpret tumor-cell killing, T-cell activation, cytokine-release, proliferation, immune-phenotyping, dose-response, time-course, and serial-killing studies.
• Quantify the impact of target density, antigen heterogeneity, effector-to-target ratio, affinity, avidity, epitope, valency, and molecular format on TCE activity and selectivity.
• Independently troubleshoot complex or inconsistent datasets and implement experiments that identify root causes and resolve uncertainty.
• Maintain rigorous experimental records and ensure data integrity, reproducibility, and appropriate statistical analysis.

2. Assay Strategy and Technical Leadership

• Own the development and qualification of robust, quantitative, and decision-enabling assay cascades for assigned TCE programs or platform workstreams.
• Establish quantitative flow-cytometry methods for target expression, immune-cell phenotyping, receptor occupancy, and related pharmacodynamic endpoints where appropriate.
• Design assays that differentiate closely related molecules and establish structure-function relationships rather than only demonstrate activity.
• Set technical standards, develop protocols, transfer methods, and coach scientists in assay execution, data analysis, and troubleshooting.
• Review raw data and experimental design from internal scientists and CROs, ensuring that conclusions are scientifically supported.

3. Molecule Characterization and Program Contribution

• Lead defined biology workstreams within one or more TCE discovery programs and deliver the data packages required for project decisions and milestones.
• Partner with antibody discovery and protein-engineering colleagues to guide optimization of tumor-target binding, CD3 engagement, valency, format, epitope, potency, cytokine profile, and tumor selectivity.
• Integrate functional biology, molecular properties, pharmacology, and translational evidence to support molecule ranking, lead selection, and risk assessment.
• Identify key scientific gaps, propose practical mitigation plans, and communicate recommendations clearly to project teams and scientific review forums.
• Contribute to target product hypotheses, decision criteria, study prioritization, and progression recommendations under the direction of the program bioscience lead.

4. Translational and Mechanistic Studies

• Design and execute mechanistic studies addressing target abundance, antigen heterogeneity, immune-cell state, resistance, combination strategies, and durability of response.
• Evaluate TCE activity in primary cells, patient-derived materials, complex co-cultures, organoid, or ex vivo systems where these models add decision value.
• Contribute to biomarker and patient-selection hypotheses by linking target expression and immune context with functional response.
• Work with pharmacology, safety, DMPK, and translational colleagues to connect in vitro findings with in vivo efficacy, pharmacodynamics, cytokine risk, and on-target, off-tumor considerations.
• Support preparation of robust preclinical packages for lead optimization, candidate nomination, and progression toward clinical development.

5. Matrix, External, and Team Leadership

• Operate as a scientific workstream leader within multidisciplinary teams spanning protein engineering, antibody discovery, oncology biology, translational science, safety, pharmacology, DMPK, and data science.
• Plan and oversee selected CRO or external-partner studies, including protocol design, technical transfer, milestone tracking, data review, and troubleshooting.
• Mentor junior scientists through experimental planning, bench coaching, data interpretation, and scientific communication, without requiring formal line-management responsibility.
• Present data, conclusions, risks, and recommendations at project-team and scientific-review meetings with an appropriate level of clarity and challenge.
• Contribute to publications, patents, external collaborations, competitive intelligence, and evaluation of emerging TCE technologies.

Essential Qualifications and Experience

• PhD in Immunology, Cancer Biology, Cell Biology, Pharmacology, Molecular Biology, or a related discipline, with relevant postdoctoral and/or industry experience.
• Strong hands-on expertise in T-cell biology, tumor immunology, immune-mediated cytotoxicity, and mammalian cell-based functional assays.
• Demonstrated experience with TCEs, bispecific or multispecific antibodies, or other immune-cell-redirecting therapeutics.
• Advanced practical expertise in primary human immune-cell culture and multiparameter flow cytometry.
• Proven ability to independently design, execute, troubleshoot, and interpret complex experiments and to convert findings into actionable project recommendations.
• Experience developing quantitative assay cascades and differentiating molecules based on mechanism, potency, selectivity, cytokine profile, and translational relevance.
• Ability to lead a defined scientific workstream, influence matrix teams, and deliver against project milestones with limited supervision.
• Fluency in spoken and written English, with the ability to participate confidently in scientific discussions, prepare clear documentation, and deliver effective presentations.
• Excellent communication and interpersonal skills, with demonstrated ability to communicate complex scientific concepts, align stakeholders, influence decisions, and collaborate effectively in a complex, cross-functional, and multicultural environment.

Preferred Qualifications

• Experience supporting TCE programs through lead optimization, candidate nomination, or IND-enabling preparation.
• Expertise in antigen-density biology, affinity and avidity tuning, epitope selection, molecular-format comparison, receptor occupancy, or cytokine-management strategies.
• Experience with serial-killing assays, complex co-culture systems, patient-derived samples, organoids, ex vivo tumor models, or high-dimensional immune profiling.
• Experience commissioning and scientifically overseeing CRO studies or external collaborations.
• Familiarity with in vivo pharmacology and the integration of in vitro potency, PK, pharmacodynamics, efficacy, and safety findings.
• A record of scientific contribution through publications, patents, conference presentations, or advancement of industry discovery programs.

Date Posted

Closing Date

AstraZeneca embraces diversity and equality of opportunity.  We are committed to building an inclusive and diverse team representing all backgrounds, with as wide a range of perspectives as possible, and harnessing industry-leading skills.  We believe that the more inclusive we are, the better our work will be.  We welcome and consider applications to join our team from all qualified candidates, regardless of their characteristics.  We comply with all applicable laws and regulations on non-discrimination in employment (and recruitment), as well as work authorization and employment eligibility verification requirements.