The Intriguing History of Cancer Immunotherapy

Abstract

Immunotherapy is often perceived as a relatively recent advance. In reality, however, one should be looking for the beginnings of cancer immunotherapy under different names as far as in the Antiquity. The first scientific attempts to modulate patients' immune systems to cure cancer can be attributed to two German physicians, Fehleisen and Busch, who independently noticed significant tumor regression after erysipelas infection. The next significant advances came from William Bradley Coley who is known today as the Father of Immunotherapy. It was Coley who first attempted to harness the immune system for treating bone cancer in 1891. His achievements were largely unnoticed for over fifty years, and several seminal discoveries in the field of Immunology, such as the existence of T cells and their crucial role in immunity in 1967, stepped up the research toward cancer immunotherapy known today. The following paper tracks cancer immunotherapy from its known beginnings up until recent events, including the 2018 Nobel Prize award to James Allison and Tasuku Honjo for their meticulous work on checkpoint molecules as potential therapeutic targets. That work has led to the successful development of new checkpoint inhibitors, CAR T-cells and oncolytic viruses and the pace of such advances brings the highest hope for the future of cancer treatment.

PTEN Function at the Interface between Cancer and Tumor Microenvironment: Implications for Response to Immunotherapy

“…The recognition of the biological role and therapeutic potential of immune checkpoint blockade (through CTLA-4 and PD-1 targeting) has revolutionized our approach to cancer immunotherapy, as also highlighted by the 2018 Nobel Prize award [11,37]. Many different monoclonal antibodies (mAb) targeting CTLA-4, PD-1, or PD ligand (PD-L)1, such as ipilumumab and nivolumab, pembrolizumab, atezolizumab, durvalumab and avelumab, have been approved for the treatment of specific cancers [25,38,39].…”

“…Immune escape represents one of the hallmarks of cancer and can be determined by a combination of relatively low cancer cell immunogenicity and tumor-dependent immunosuppression [9]. The recognition of the role of immune checkpoints, particularly cytotoxic T-lymphocyte antigen (CTLA)-4 and programmed cell death (PD)-1, has shed new light on the mechanisms of negative regulation of the immune system and opened a new era in the clinical application of immunotherapy in cancer [10,11]. In such a complex scenario, the continuous bidirectional interactions between cancer cells and infiltrating immune/inflammatory cells are dictated, at least in part, by the genetic background of the different cancerous and non-cancerous components.…”

Colorectal Cancer Immunotherapy: Options and Strategies

“…Furthermore, due to its unreproducible results, Coley's toxin was opposed by most of the health practitioners. Surgery remained the most preferable way to treat cancer during that time (27).…”

A Significant Question in Cancer Risk and Therapy: Are Antibiotics Positive or Negative Effectors? Current Answers and Possible Alternatives

“…Interestingly, similarly to bacterial infections, cancer treatments were also based on the "humor theory" through the mid-19th century, with progressive incorporation of improved surgical techniques [80,81]. It was not until the 1890s that X-rays were used as the first form of radiotherapy [82], around 1940 for the beginning of chemotherapy [83], after 1970 for the use of antibodies [84], and much more recently for the use of protocols targeting the immune checkpoints [85], bringing immunotherapy to the first line of currently available anticancer therapies. It is worth mentioning this point that the term "chemotherapy" was first introduced in the early 1900s by the German biochemist Paul Ehrlich to refer to the use of chemicals to treat diseases, in particular infectious diseases [83].…”