He engaged in medical research in the early fifties, and took an internship in immunology and oncology in the Memorial Sloan–Kettering Cancer Center, New York.

In November 1958, Mathé performed the first bone marrow graft between unrelated donors and hosts ever made in the world, in order to save four Yugoslav nuclear researchers who had been accidentally irradiated.

He also taught experimental oncology at the University of Paris (1966 to 1990), created and managed (from 1980 to 1988) the Service des Maladies Sanguines et Tumorales in the Hôpital Paul-Brousse where he blended research and therapy with groundbreaking methods and results in chemotherapy and immunotherapy to develop polytherapies adapted to individual cases.

which was formally and legally established in 1962 by a group of European visionaries including Henri Tagnon, Silvio Garattini, Dirk van Bekkum, among others.

He also played a crucial role in the creation of the ARC in 1962, the INSERM in 1964, the CIRC in 1965, and the SMIC in 1975 which became the European Society for Medical Oncology (ESMO) in 1980.

Dr. Brian Bolwell, chief of hematology at the Cleveland Clinic noted that Dr. Mathé had proved an important principle: "You can cure an incurable leukemia patient.

", and had developed both a technique and an important term, "adoptive immunotherapy," to describe how a person's own immune system can be used to combat cancer and other diseases.

[1] Dr. Joseph H. Antin, chief of stem cell transplantation at the Dana–Farber Cancer Institute in Boston, summed up Mathé's work: "It was quite a leap of scientific genius.