The immuno-oncology framework

Figures & data

Figure 1. The immuno-oncology framework provides a set of methodological improvements for the development of cancer immunotherapies, which are tailored to this class of therapies. Each component addresses a relevant piece of the drug development process and was evolved out of a community consensus approach through the immunotherapy organizations CIC and CIMT. The framework is expected to expand with ongoing evolution of the field.

Table 1. The framework for immuno-oncology: Solutions for common challenges

Challenge	Solution	Perspective	Refs.
Use of chemotherapy principles for clinical development of immunotherapy	New clinical development paradigm for immunotherapy with key components: (1) development phases for proof-of-principle and efficacy; (2) toxicity screening, (3) measurement of biologic activity, (4) immune response measurement in clinical trials, (5) dose and schedule, (6) developmental decision points, (7) trial design, (8) clinical endpoints, (9) combination therapy	A defined and reproducible path for adequate development of cancer immunotherapies	5
Clinical kinetics of immunotherapies not reflected by conventional endpoints	Adjustment of endpoints to immunotherapy biology	More complete detection of efficacy	9
No recognized system to measure all patterns of immunotherapy clinical activity	Immunotherapy response criteria derived from RECIST and WHO: Immune-related Response Criteria (irRC)	Capture all clinical activity patterns for a reliable assessment of activity signals in early trials	10
High data variability for immune monitoring in multi-center trials	Harmonization guidelines and quality assurance for immune monitoring assays	Enable reproducible investigation of immune response as biomarkers in clinical development. Subsequently, enable clinical qualification and investigate surrogacy.	28–31
Inconsistent reporting of immune monitoring results in scientific publications	Reporting framework for scientific publications: Minimal Information About T-cell Assays (MIATA)	Transparency of results and comparability across centers and trials	11, 12
Limited integration and distribution of key scientific and developmental knowledge	Focused scientific exchange between academia, industry and regulators through meetings and workshops	Broad access of new and evolving knowledge and processes across the community	www.cancerresearch.org/consortium www.cimt.eu
Absence of regulatory guidance for cancer immunotherapy development	Broad scientific exchange with participation of regulators to support guidance document development	Credible development criteria for prospective use	13, 14
Additional components	Based on community need	Evolution of framework

Table 1 adapted from reference 4, with permission.

Hoos A, Parmiani G, Hege K, Sznol M, Loibner H, Eggermont A, et al. A clinical development paradigm for cancer vaccines and related biologics. J Immunother 1997; 30:1 - 15

 Web of Science ®Google Scholar

Hoos A, Eggermont AM, Janetzki S, Hodi FS, Ibrahim R, Anderson A, et al. Improved endpoints for cancer immunotherapy trials. J Natl Cancer Inst 2010; 102:1388 - 97; http://dx.doi.org/10.1093/jnci/djq310; PMID: 20826737

 PubMed Web of Science ®Google Scholar

Wolchok JD, Hoos A, O’Day S, Weber JS, Hamid O, Lebbe´ C, et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res 2009; 15:7412 - 20; http://dx.doi.org/10.1158/1078-0432.CCR-09-1624; PMID: 19934295

 PubMed Web of Science ®Google Scholar

Janetzki S, Panageas KS, Ben-Porat L, Boyer J, Britten CM, Clay TM, et al, Elispot Proficiency Panel of the CVC Immune Assay Working Group. Results and harmonization guidelines from two large-scale international Elispot proficiency panels conducted by the Cancer Vaccine Consortium (CVC/SVI). Cancer Immunol Immunother 2008; 57:303 - 15; http://dx.doi.org/10.1007/s00262-007-0380-6; PMID: 17721781

 PubMed Web of Science ®Google Scholar

Britten CM, Gouttefangeas C, Welters MJ, Pawelec G, Koch S, Ottensmeier C, et al. The CIMT-monitoring panel: a two-step approach to harmonize the enumeration of antigen-specific CD8+ T lymphocytes by structural and functional assays. Cancer Immunol Immunother 2008; 57:289 - 302; http://dx.doi.org/10.1007/s00262-007-0378-0; PMID: 17721783

 PubMed Web of Science ®Google Scholar

Britten CM, Janetzki S, Ben-Porat L, Clay TM, Kalos M, Maecker H, et al, HLA-peptide Multimer Proficiency Panel of the CVC-CRI Immune Assay Working Group. Harmonization guidelines for HLA-peptide multimer assays derived from results of a large scale international proficiency panel of the Cancer Vaccine Consortium. Cancer Immunol Immunother 2009; 58:1701 - 13; http://dx.doi.org/10.1007/s00262-009-0681-z; PMID: 19259668

 PubMed Web of Science ®Google Scholar

Attig S, Price L, Janetzki S, Kalos M, Pride M, McNeil L, et al, CRI-CIC Assay Working Group. A critical assessment for the value of markers to gate-out undesired events in HLA-peptide multimer staining protocols. J Transl Med 2011; 9:108; http://dx.doi.org/10.1186/1479-5876-9-108; PMID: 21745365

 PubMed Web of Science ®Google Scholar

Janetzki S, Britten CM, Kalos M, Levitsky HI, Maecker HT, Melief CJ, et al. “MIATA”-minimal information about T cell assays. Immunity 2009; 31:527 - 8; http://dx.doi.org/10.1016/j.immuni.2009.09.007; PMID: 19833080

 PubMed Web of Science ®Google Scholar

Britten CM, Janetzki S, van der Burg SH, Huber C, Kalos M, Levitsky HI, et al. Minimal information about T cell assays: the process of reaching the community of T cell immunologists in cancer and beyond. Cancer Immunol Immunother 2011; 60:15 - 22; http://dx.doi.org/10.1007/s00262-010-0940-z; PMID: 21080166

 PubMed Web of Science ®Google Scholar

Guidance for industry: Clinical Considerations for Therapeutic Cancer Vaccines. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research, September 2009. http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Vaccines/UCM182826.pdf.

 Google Scholar

Concept paper on the need to revise the guideline on the evaluation of anticancer medicinal products in man. European Medicines Agency. July 2010. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/09/WC500096730.pdf.

 Google Scholar

Hoos A, Britten CM, Huber C, O’Donnell-Tormey J. A methodological framework to enhance the clinical success of cancer immunotherapy. Nat Biotechnol 2011; 29:867 - 70; http://dx.doi.org/10.1038/nbt.2000; PMID: 21997622

 PubMed Web of Science ®Google Scholar