The human IL-15 superagonist ALT-803 directs SIV-specific CD8+ T cells into B-cell follicles

Gabriela M. Webb; Shengbin Li; Gwantwa Mwakalundwa; Joy M. Folkvord; Justin M. Greene; Jason S. Reed; Jeffery J. Stanton; Alfred W. Legasse; Theodore Hobbs; Lauren D. Martin; Byung S. Park; James B. Whitney; Emily K. Jeng; Hing C. Wong; Douglas F. Nixon; R. Brad Jones; Elizabeth Connick; Pamela J. Skinner; Jonah B. Sacha

doi:10.1182/bloodadvances.2017012971

The human IL-15 superagonist ALT-803 directs SIV-specific CD8+ T cells into B-cell follicles

Gabriela M. Webb, Shengbin Li, Gwantwa Mwakalundwa, Joy M. Folkvord, Justin M. Greene, Jason S. Reed, Jeffery J. Stanton, Alfred W. Legasse, Theodore Hobbs, Lauren D. Martin, Byung S. Park, James B. Whitney, Emily K. Jeng, Hing C. Wong, Douglas F. Nixon, R. Brad Jones, Elizabeth Connick, Pamela J. Skinner, Jonah B. Sacha

Research output: Contribution to journal › Article › peer-review

64 Scopus citations

Abstract

Sequestering of latent HIV in follicular helper T cells within B-cell follicles that largely exclude cytotoxic T cells is a major barrier to cellular immune-based approaches to eradicate HIV. Here, we show that the clinical-grade human interleukin-15 (IL-15) superagonist ALT-803 activates and redirects simian immunodeficiency virus (SIV)-specific CD81 T cells from the peripheral blood into B-cell follicles. In agreement with the increased trafficking of SIVspecific cytotoxic T cells to sites of cryptic viral replication, lymph nodes of elite controlling macaques contained fewer cells expressing SIV RNA or harboring SIV DNA post-ALT-803 treatment. These data establish ALT-803 as an immunotherapeutic for HIV and other chronic viral pathogens that evade host immunity by persisting in B-cell follicles.

Original language	English (US)
Pages (from-to)	76-84
Number of pages	9
Journal	Blood Advances
Volume	2
Issue number	2
DOIs	https://doi.org/10.1182/bloodadvances.2017012971
State	Published - Jan 23 2018

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Publisher Copyright:
© 2018 by The American Society of Hematology.

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10.1182/bloodadvances.2017012971

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Webb, G. M., Li, S., Mwakalundwa, G., Folkvord, J. M., Greene, J. M., Reed, J. S., Stanton, J. J., Legasse, A. W., Hobbs, T., Martin, L. D., Park, B. S., Whitney, J. B., Jeng, E. K., Wong, H. C., Nixon, D. F., Jones, R. B., Connick, E., Skinner, P. J., & Sacha, J. B. (2018). The human IL-15 superagonist ALT-803 directs SIV-specific CD8+ T cells into B-cell follicles. Blood Advances, 2(2), 76-84. https://doi.org/10.1182/bloodadvances.2017012971

Webb, GM, Li, S, Mwakalundwa, G, Folkvord, JM, Greene, JM, Reed, JS, Stanton, JJ, Legasse, AW, Hobbs, T, Martin, LD, Park, BS, Whitney, JB, Jeng, EK, Wong, HC, Nixon, DF, Jones, RB, Connick, E, Skinner, PJ & Sacha, JB 2018, 'The human IL-15 superagonist ALT-803 directs SIV-specific CD8+ T cells into B-cell follicles', Blood Advances, vol. 2, no. 2, pp. 76-84. https://doi.org/10.1182/bloodadvances.2017012971

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abstract = "Sequestering of latent HIV in follicular helper T cells within B-cell follicles that largely exclude cytotoxic T cells is a major barrier to cellular immune-based approaches to eradicate HIV. Here, we show that the clinical-grade human interleukin-15 (IL-15) superagonist ALT-803 activates and redirects simian immunodeficiency virus (SIV)-specific CD81 T cells from the peripheral blood into B-cell follicles. In agreement with the increased trafficking of SIVspecific cytotoxic T cells to sites of cryptic viral replication, lymph nodes of elite controlling macaques contained fewer cells expressing SIV RNA or harboring SIV DNA post-ALT-803 treatment. These data establish ALT-803 as an immunotherapeutic for HIV and other chronic viral pathogens that evade host immunity by persisting in B-cell follicles.",

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AU - Greene, Justin M.

AU - Reed, Jason S.

AU - Stanton, Jeffery J.

AU - Legasse, Alfred W.

AU - Hobbs, Theodore

AU - Martin, Lauren D.

AU - Park, Byung S.

AU - Whitney, James B.

AU - Jeng, Emily K.

AU - Wong, Hing C.

AU - Nixon, Douglas F.

AU - Jones, R. Brad

AU - Connick, Elizabeth

AU - Skinner, Pamela J.

AU - Sacha, Jonah B.

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N2 - Sequestering of latent HIV in follicular helper T cells within B-cell follicles that largely exclude cytotoxic T cells is a major barrier to cellular immune-based approaches to eradicate HIV. Here, we show that the clinical-grade human interleukin-15 (IL-15) superagonist ALT-803 activates and redirects simian immunodeficiency virus (SIV)-specific CD81 T cells from the peripheral blood into B-cell follicles. In agreement with the increased trafficking of SIVspecific cytotoxic T cells to sites of cryptic viral replication, lymph nodes of elite controlling macaques contained fewer cells expressing SIV RNA or harboring SIV DNA post-ALT-803 treatment. These data establish ALT-803 as an immunotherapeutic for HIV and other chronic viral pathogens that evade host immunity by persisting in B-cell follicles.

AB - Sequestering of latent HIV in follicular helper T cells within B-cell follicles that largely exclude cytotoxic T cells is a major barrier to cellular immune-based approaches to eradicate HIV. Here, we show that the clinical-grade human interleukin-15 (IL-15) superagonist ALT-803 activates and redirects simian immunodeficiency virus (SIV)-specific CD81 T cells from the peripheral blood into B-cell follicles. In agreement with the increased trafficking of SIVspecific cytotoxic T cells to sites of cryptic viral replication, lymph nodes of elite controlling macaques contained fewer cells expressing SIV RNA or harboring SIV DNA post-ALT-803 treatment. These data establish ALT-803 as an immunotherapeutic for HIV and other chronic viral pathogens that evade host immunity by persisting in B-cell follicles.

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The human IL-15 superagonist ALT-803 directs SIV-specific CD8+ T cells into B-cell follicles

Abstract

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