Deep sequencing of the T cell receptor visualizes reconstitution of T cell immunity in mogamulizumab-treated adult T cell leukemia

• Published in: Oncoimmunology Vol. 7; no. 3; p. e1405204
• Main Authors: Shindo, Takero, Kitaura, Kazutaka, Ureshino, Hiroshi, Kamachi, Kazuharu, Miyahara, Masaharu, Doi, Kazuko, Watanabe, Tatsuro, Sueoka, Eisaburo, Shin-I, Tadasu, Suzuki, Ryuji, Kimura, Shinya
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.01.2018; Taylor & Francis Group
• Subjects: adult t cell leukemia; Brief Report; immune reconstitution; mogamulizumab; next generation sequencing; t cell receptor; immune reconstitution; mogamulizumab; T cell receptor; adult T cell leukemia; next generation sequencing
• ISSN: 2162-4011; 2162-402X; 2162-402X
• DOI: 10.1080/2162402X.2017.1405204

Although the anti-CCR4 antibody mogamulizumab (moga) shows striking antitumor activity against adult T cell leukemia (ATL), it can also cause fatal immunological pathology such as severe skin rash and graft-versus-host disease, which might be attributed to depletion of CCR4 regulatory T cells. We previously showed that next generation sequencing enables precise analysis of the T cell receptor (TCR) repertoire, and we here used the technique to reveal the immunological dynamics in moga-treated ATL patients. Treatment with moga resulted in remarkable reduction or elimination of clonal cells, and enhanced reconstitution of non-tumor polyclonal CD4 T cells and oligoclonal CD8 T cells. Interestingly, cutaneous T cells infiltrating moga-related skin rashes did not share the same major clones in peripheral blood, which minimizes the possibility of cross-reaction. Thus, deep sequencing of the TCR can reveal the immune reconstitution of moga-treated ATL and provides powerful insights into its mode of action.