How Non-invasive in vivo Cell Tracking Supports the Development and Translation of Cancer Immunotherapies

Abstract

Immunotherapy is a relatively new treatment regimen for cancer, and it is based on the modulation of the immune system to battle cancer. Immunotherapies can be classified as either molecular or cell-based immunotherapies, and both types have demonstrated promising results in a growing number of cancers. Indeed, several immunotherapies representing both classes are already approved for clinical use in oncology. While spectacular treatment successes have been reported, particularly for so-called immune checkpoint inhibitors and certain cell-based immunotherapies, they have also been accompanied by a variety of severe, sometimes life-threatening side effects. Furthermore, not all patients respond to immunotherapy. Hence, there is the need for more research to render these promising therapeutics more efficacious, more widely applicable, and safer to use. Whole-body in vivo imaging technologies that can interrogate cancers and/or immunotherapies are highly beneficial tools for immunotherapy development and translation to the clinic. In this review, we explain how in vivo imaging can aid the development of molecular and cell-based anti-cancer immunotherapies. We describe the principles of imaging host T-cells and adoptively transferred therapeutic T-cells as well as the value of traceable cancer cell models in immunotherapy development. Our emphasis is on in vivo cell tracking methodology, including important aspects and caveats specific to immunotherapies. We discuss a variety of associated experimental design aspects including parameters such as cell type, observation times/intervals, and detection sensitivity. The focus is on non-invasive 3D cell tracking on the whole-body level including aspects relevant for both preclinical experimentation and clinical translatability of the underlying methodologies.

Spatiotemporal in vivo tracking of polyclonal human regulatory T cells (Tregs) reveals a role for innate immune cells in Treg transplant recruitment

“…Long-term cell tracking can be achieved through indirect cell labeling, which involves genetic engineering to express a reporter and render the cells in vivo traceable by repeat imaging. 16 , 22 Treg in vivo dynamics were assessed using bioluminescence approaches. 23 , 24 , 25 However, bioluminescence imaging is not translatable to the clinic because of the non-human nature of luciferases, which also require luminogenic substrate administration, and the added disadvantages of optical imaging at depth (absorption, scatter) precluding reliable quantification.…”

The Future of Regulatory T Cell Therapy: Promises and Challenges of Implementing CAR Technology

“…The field of in vivo cell tracking has re-gained new momentum through the development of adoptive cell therapies. The various cell tracking methodologies including a variety of experimental design considerations and caveats have recently been comprehensively reviewed (98), also in the context of tracking T cell therapies (99). Fundamentally, cells require labeling to visualize them in vivo using technologies with exquisite sensitivities.…”

“…However, radio-damage as a consequence of radioisotope incorporation into cells must be assessed, particularly in cell types such as T cells that are routinely ablated using radiation. Therefore, careful dosimetry considerations are required to assess both the preclinical and clinical feasibility of Treg tracking via this route [for caveats see (98)].…”

“…Non-invasive radionuclide imaging by single photon emission computed tomography (SPECT) or positron emission tomography (PET) offers excellent sensitivity with absolute quantification and true 3D information while being translatable to the clinic. Labels can be introduced into cells via two fundamentally different methodologies, direct and indirect cell labeling ( 98 ).…”

A Minimal PKPD Interaction Model for Evaluating Synergy Effects of Combined NSCLC Therapies

“…It has been shown that combination therapy in cancer leads to synergic effects with improved outcome [ 1 , 2 ]. The SBRT (stereotactic body radiotherapy) is prevalent in lung cancer treatment as it is most patient friendly in terms of side effects, while proving to have excellent results [ 3 , 4 , 5 ].…”