NEW YORK, September 22 — Cancer immunotherapy, the field that turns a patient’s own immune system against tumors, now stands as the fourth pillar of cancer care alongside surgery, radiation and chemotherapy. Its story stretches back well over a century, and the last three decades have produced the approvals that moved it from laboratory theory to bedside treatment. The foundations were laid in 1891, when New York surgeon William B.
Coley injected bacteria into inoperable tumors and recorded occasional regressions — an early hint that the immune system could be enlisted against cancer. The modern toolkit began to take shape in 1975, when César Milstein and Georges Köhler developed monoclonal antibody technology, enabling lab-made antibodies that could be engineered to target cancer cells.
In 1984, the FDA approved muromonab-CD3, the first therapeutic monoclonal antibody, for transplant rejection — proof that the platform could work in patients. Then in 1997, rituximab became the first monoclonal antibody approved for cancer, targeting CD20 on B-cell lymphomas.
Checkpoint inhibition changes the field
A major conceptual breakthrough came in 1996, when James P. Allison showed that blocking CTLA-4 — an immune checkpoint that brakes T cells — could unleash antitumor immunity in mice. That work translated into the clinic in 2011, when the FDA approved ipilimumab (Yervoy), an anti-CTLA-4 antibody, for metastatic melanoma.
It was the first checkpoint inhibitor. Three years later, pembrolizumab (Keytruda) and nivolumab (Opdivo), both anti-PD-1 antibodies, were approved for melanoma; PD-1 blockade has since been cleared for dozens of cancer types.
In 2018, Allison and Tasuku Honjo received the Nobel Prize in Physiology or Medicine for checkpoint inhibition. Engineered cell therapies followed a parallel path. In 2017, the FDA approved tisagenlecleucel (Kymriah) for pediatric acute lymphoblastic leukemia — the first CAR-T therapy, in which a patient’s T cells are genetically engineered with a chimeric antigen receptor to attack CD19-positive cancer cells.
Later CAR-T approvals include axicabtagene ciloleucel (Yescarta, 2017) for large B-cell lymphoma and lisocabtagene maraleucel (Breyanzi, 2021). As of 2024, six CAR-T therapies are FDA-approved, all for blood cancers; solid tumors remain largely resistant.
In 2020, the Nobel Prize in Chemistry went to Emmanuelle Charpentier and Jennifer Doudna for CRISPR-Cas9 gene editing, a tool now used to engineer immune cells.
Newer approaches and the cost question
The solid-tumor barrier has begun to crack. In 2023, the FDA granted accelerated approval to afami-cel (Tecelra) for synovial sarcoma — the first engineered T-cell therapy for a solid tumor. Also in 2023, mRNA cancer vaccine candidates entered trials.
Moderna and Merck’s mRNA-4157 (V940), a personalized neoantigen therapy, was tested with pembrolizumab in high-risk melanoma in the phase 2b KEYNOTE-942 trial, while BioNTech’s autogene cevumeran was tested in pancreatic cancer. In 2024, the FDA approved lifileucel (Amtagvi), the first tumor-infiltrating lymphocyte (TIL) therapy, for advanced melanoma.
Immunotherapy does not work for all patients. Response rates vary by cancer type and biomarker, such as PD-L1 expression or MSI-high status. It can also cause immune-related adverse events — colitis, pneumonitis, thyroiditis and cytokine release syndrome — managed with steroids or tocilizumab.
And costs are high. CAR-T list prices exceed $400,000 per infusion in the US, while checkpoint inhibitors can cost over $100,000 annually.
The encouraging part is the direction of travel. A field that began with a nineteenth-century surgeon injecting bacteria into tumors now has checkpoint inhibitors cleared across dozens of cancer types, engineered T cells reaching a solid tumor, and personalized mRNA vaccines in mid-stage trials. Patients should talk to their doctor about whether any of these options, or a clinical trial, fits their diagnosis. Consult your doctor for medical advice.
