Adoptive transfer of bryostatin-activated tumor-sensitized lymphocytes prevents or destroys tumor metastases without expansion in vitro

Martin Fleming, Harry D. Bear, Kenneth Lipshy, Paul J. Kostuchenko, Diana Portocarero, Andrew W.J. McFadden, Sandra K. Barrett

Research output: Contribution to journalArticle

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Abstract

Because the requirement for long-term cell culture can make adoptive cellular immunotherapy cumbersome, experiments were designed to determine whether smaller numbers of tumor-sensitized T cells activated briefly with bryostatin 1 and ionomycin (B/I) could be returned immediately to recipient mice without in vitro expansion and still have an anti-tumor effect in vivo. Popliteal tumor-draining lymph nodes (DLNs) from mice bearing progressive MCA-105 and MCA-203 footpad sarcomas were harvested and treated for 18 h with B/I. These cells were then washed and transferred immediately to naive C57Bl/6 mice. In some experiments, these mice were irradiated (500 rads) before adoptive transfer and were given interleukin-2 (IL-2, 7,500 IU i.p., b.i.d. for 3 days) after receiving the activated lymphocytes. Recipient mice were challenged with sarcoma cells (4 x 105i.v.) 6 to 32 days after receiving the activated lymphocytes. Mice receiving 106B/I-activated lymphocytes before tumor challenge had significantly fewer metastases than did controls. This protective effect did not require exogenous IL-2 or host irradiation. Using Thy-1 congenic donors, it was shown that B/I-activated T cells expanded in recipients when IL-2 was also given, and these cells were a prominent component (15% of total cells) in the infiltrates found in the lungs of mice 7 days after i.v. tumor challenge. Combining these B/I-“pulsed” cells with cyclophosphamide (CYP) and IL-2 to treat mice with established (3-day) metastases resulted in significant reduction in pulmonary nodules, with complete regression in many of the treated mice, which was rarely seen with CYP alone or with CYP + IL-2. Thus, adoptive transfer of tumor-sensitized, B/I-activated DLN cells confers protection against i.v. tumor challenge, without prior in vitro expansion of the effector cells. Phenotyping studies demonstrate that donor cells activated with B/I do expand in recipient mice after adoptive transfer and can move to sites of tumor. Moreover, these cells can mediate a therapeutic effect on established tumor metastases, when combined with chemotherapy.

Original languageEnglish (US)
Pages (from-to)147-155
Number of pages9
JournalJournal of Immunotherapy
Volume18
Issue number3
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

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Bryostatins
Adoptive Transfer
Lymphocytes
Neoplasm Metastasis
Ionomycin
Interleukin-2
Neoplasms
Cyclophosphamide
Sarcoma
Lymph Nodes
In Vitro Techniques
T-Lymphocytes
Adoptive Immunotherapy
Interleukin-7
Lung
Cytoprotection
Therapeutic Uses
Cell Culture Techniques

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

Cite this

Adoptive transfer of bryostatin-activated tumor-sensitized lymphocytes prevents or destroys tumor metastases without expansion in vitro. / Fleming, Martin; Bear, Harry D.; Lipshy, Kenneth; Kostuchenko, Paul J.; Portocarero, Diana; McFadden, Andrew W.J.; Barrett, Sandra K.

In: Journal of Immunotherapy, Vol. 18, No. 3, 01.01.1995, p. 147-155.

Research output: Contribution to journalArticle

Fleming, Martin ; Bear, Harry D. ; Lipshy, Kenneth ; Kostuchenko, Paul J. ; Portocarero, Diana ; McFadden, Andrew W.J. ; Barrett, Sandra K. / Adoptive transfer of bryostatin-activated tumor-sensitized lymphocytes prevents or destroys tumor metastases without expansion in vitro. In: Journal of Immunotherapy. 1995 ; Vol. 18, No. 3. pp. 147-155.
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