# Cell therapy for brain tumors: The first 60 years

## TL;DR

This paper reviews 60 years of clinical trials using cell-based immunotherapies for brain tumors, highlighting their safety and occasional effectiveness.

## Contribution

The paper provides a comprehensive historical review of adoptive cell therapies for brain tumors, summarizing clinical experiences and findings.

## Key findings

- Early cell therapies showed safety and occasional durable antitumor responses.
- Combining cell therapies with conventional treatments improved outcomes in some cases.
- Various cell types, including CAR T cells, have been tested over six decades.

## Abstract

Primary brain tumors remain among the most lethal cancers, but immunotherapy holds immense potential to overcome limitations of current standard treatment modalities. Since the late 1960s, early-phase clinical trials have iteratively tested cellular immunotherapies for the treatment of brain tumors. Six decades ago, in the earliest studies, brain tumor patients were treated with infusions of nonspecific leukocytes, peripheral blood mononuclear cells (PBMCs), and bone marrow cells. These earliest studies demonstrated safety and occasional durable antitumor responses, particularly when cell therapies were combined with conventional modalities or administered in the upfront setting. These early cell therapy approaches were chronologically followed by lymphokine-activated killer (LAK) cells, tumor-infiltrating lymphocytes (TILs), ex vivo nonspecifically expanded and antigen-specific T cells, natural killer (NK) cells, and chimeric antigen receptor (CAR) T cells. In this historical review, we summarize the clinical experience with adoptive cell therapies for brain tumors and review key findings from published clinical studies.

Cellular immunotherapies have been tested for the treatment of primary brain tumors since 1968, with clinical responses observed, albeit limited and inconsistent, from the earliest studies. Mehta et al. review clinical experience with adoptive cell therapies for brain tumors, highlighting key findings from published clinical studies.