Hurdles Preventing Cancer Immunotherapy from Reaching Full Potential

A recent study analyzed different reasons for delays between preclinical and clinical trials for cancer immunotherapy and how to overcome such hurdles.

Cancer research has led to insights, reagents, drugs, and clinical protocols that can improve outcomes, especially when it comes to cancer immunotherapy. There has been, however, a slow translation from these findings into real-life benefits for patients, according to a study published in the Journal of Translational Medicine.

Researchers from 8 immunotherapy organizations met at an Immunotherapy Summit at what is now called the Society for Immunotherapy of Cancer (SITC) and identified hurdles that slow down the translation of cancer immunotherapy.

The following year, at the 25^th Annual Meeting of SITC, these groups discussed how to overcome these challenges, agreeing to collaborate to resolve this issue and provide novel, effective immunotherapy strategies.

The group identified 9 hurdles for immunotherapy:

• Limitations of Preclinical Animal Models
• Delayed Institutional, Administrative and Regulatory Approval
• Complexity of Cancer, Tumor Heterogeneity and Immune Escape
• Limited Availability of Reagents for Combination Immunotherapy Studies
• Limited Funds Available to Translate Science into Patients
• Lack of Definitive Biomarkers of Immune Response
• Conventional Response Criteria May Not Reflect the Patterns of Response to Immunotherapies
• Paucity of Translational Teams of Scientists and Clinicians
• Need to Enhance Exchange of Information Critical to Advancing the Field

Researchers believe all of these hurdles can be overcome through various approaches and techniques.

For example, researchers find that preclinical animal models have not been consistent predictors of efficacy for immunotherapy and the models do not have the genetic diversity that humans have. Researchers wonder if there are certain standards that could be suggested for using preclinical models that improve the utility and interpretation of these animal studies.

Delays in approval have shown to be a big issue as well, and in some academic institutions, researchers can wait for up to 7 months before approval. Researchers conclude that a cost-benefit analysis may be needed. It was further noted that if there is another process besides Current Good Manufacturing Practice, this could increase quality without increasing costs, as well as reducing time for approved clinical trials.

The complexity of each cancer and the ability of cells to develop resistance is a critical hurdle to the researchers. Certain cancers, such as melanoma, are not a single disease, but can be multiple diseases that can all respond differently to treatments.

Researchers suggest the characterization of tumors, before and after immunotherapy, could be a way to gain more information about certain cancers. Revising patient consent documents for biomarker development is also a consideration to learn more about the complexity of certain cancers, according to the study.

Preclinical trials show significantly improved outcomes when immunotherapy is combined with other agents, but this may add additional complexities for the drug developer and the patient.

The study noted that a consensus among researchers developing a strategy that provides an optimal biologically active dose would be helpful and likely aid the implementation of combination therapy.

Obtaining funds to initiate clinical trials after success with preclinical trials is also a hurdle. Researchers believe this funding issue could be resolved through communicating how the investment would be able to help economies and human health.

Currently, there are a lack of validated biomarkers that monitor the development of an immune response after immunotherapy, which also is a critical hurdle, according to the study.

Standardized processes, internal controls, and improved reporting could potentially improve the identification of biomarkers, the study noted.

Researchers also discuss how response to therapy criteria was developed with cytotoxic therapies. Certain patients may not be identified as responding to therapy, even though they had a reduction in tumor burdens. A discussion of changing the response criteria to better fit immunotherapy needs to occur to remedy this hurdle, the authors wrote.

A scarcity of researchers translating new technologies into promising immunotherapies is discussed in the study. They also wrote that academic translation research teams are most likely in the best position to move their agent to clinical trials, according to the study.

Investments should be made for these academic teams and recognition would contribute to the lessening this hurdle. The last hurdle discussed is the exchange of information between research groups, since it is not as likely that a group would have all of the resources to be able to investigate, analyze, select, and implement a strategy for clinical trials.

Bringing together groups of researchers would likely let researchers collaborate with each other, the authors stated.

Researchers concluded that identifying the hurdles is an important initial step and they look forward to combining their efforts to resolve these issues.