Leukemia and Customized AAIT

Since leukemia is a cancer affecting white blood cells, and most immunotherapy strategies aim to increase the ability of white blood cells to battle cancer, leukemia has posed interesting queries to researchers in this arena. Just recently have adoptive immunotherapy strategies become available to patients stricken with leukemia. The major obstacle was the inability to isolate normal, non-leukemic cells that could target cancerous cells. Envita's unique leukemia protocol allows us to achieve just that.

Published research literature has confirmed that NKs, NKTs, and CTLs can undeniably be isolated, expanded and activated from the blood of patients diagnosed with leukemia. Although patients with acute lymphoid leukemia (ALL) or chronic lymphoid leukemia (CLL) have very few normal lymphocytes, successful expansion of NK, NKT, and CTLs was duly noted.[1-5] Likewise, these cells could also be generated from patients with acute myeloid leukemia (AML) or chronic myeloid leukemia (CML), whose lymphocytes are non-cancerous, but typically dysfunctional.[6-11] In the majority of cases, the NKs, NKTs, and CTLs expanded from leukemia patients were able to marginalize tumor cells in laboratory tests.[2-4,6-11] There is strong evidence that in acute leukemia patients who have experienced remission, the ability of their natural killer cells to defy cancer cells in laboratory tests is a strong indicator of continued remission.12 Those patients with higher natural killer cell activity had lengthier remission periods than those with lower NK activity.[12]

A recent clinical trial at renowned Mayo Clinic in Rochester, Minnesota utilized natural killer cells in patients with poor prognosis acute myeloid leukemia. 5 out of 19 patients experienced complete remissions after receiving these NK cell infusions.13 The use of natural killer cell therapy in earlier stage patients is under consideration due to these results. In other published scientific research studies, the presence of activated NK cells and other tumor-fighting immune cells have been recognized as prime factors in the response of cancer patients to drugs such as thalidomide and Gleevec.[14,15]

Envita is enhancing all published literature and producing the latest effective treatments for leukemia, thus exceeding the current limitations.


1) Ritz J. Expansion of natural killer cells for use in acute lymphoid leukemia. Haematologica. 2005 Jun;90(6):723A. 2) Torelli GF, Guarini A, Maggio R, Alfieri C, Vitale A, Foa R. Expansion of natural killer cells with lytic activity against autologous blasts from adult and pediatric acute lymphoid leukemia patients in complete hematologic remission. Haematologica. 2005 Jun;90(6):785-92.

3) Cardoso AA, Veiga JP, Ghia P, Afonso HM, Haining WN, Sallan SE, Nadler LM. Adoptive T-cell therapy for B-cell acute lymphoblastic leukemia: preclinical studies. Blood. 1999 Nov 15;94(10):3531-40.

4) Guven H, Gilljam M, Chambers BJ, Ljunggren HG, Christensson B, Kimby E, Dilber MS. Expansion of natural killer (NK) and natural killer-like T (NKT)-cell populations derived from patients with B-chronic lymphocytic leukemia (B-CLL): a potential source for cellular immunotherapy. Leukemia. 2003 Oct;17(10):1973-80.

5) Lee YK, Kay NE. Reconstitution of innate immunity in B-chronic lymphocytic leukemia: time to reconsider the possibilities. Leukemia. 2003 Oct;17(10):1945-7.

6) Linn YC, Lau LC, Hui KM. Generation of cytokine-induced killer cells from leukaemic samples with in vitro cytotoxicity against autologous and allogeneic leukaemic blasts. Br J Haematol. 2002 Jan;116(1):78-86.

7) Linn YC, Hui KM. Cytokine-induced killer cells: NK-like T cells with cytotolytic specificity against leukemia. Leuk Lymphoma. 2003 Sep;44(9):1457-62.

8) Orleans-Lindsay JK, Deru A, Craig JI, Prentice HG, Lowdell MW. In vitro co-stimulation with anti-CD28 synergizes with IL-12 in the generation of T cell immune responses to leukaemic cells; a strategy for ex-vivo generation of CTL for immunotherapy. Clin Exp Immunol. 2003 Sep;133(3):467-75.

9) Cervantes F, Pierson BA, McGlave PB, Verfaillie CM, Miller JS. Autologous activated natural killer cells suppress primitive chronic myelogenous leukemia progenitors in long-term culture. Blood. 1996 Mar 15;87(6):2476-85.

10) Verfaillie C, Miller W, Kay N, McGlave P. Adherent lymphokine-activated killer cells in chronic myelogenous leukemia: a benign cell population with potent cytotoxic activity. Blood. 1989 Aug 1;74(2):793-7.

11) Hoyle C, Bangs CD, Chang P, Kamel O, Mehta B, Negrin RS. Expansion of Philadelphia chromosome-negative CD3(+)CD56(+) cytotoxic cells from chronic myeloid leukemia patients: in vitro and in vivo efficacy in severe combined immunodeficiency disease mice. Blood. 1998 Nov 1;92(9):3318-27.

12) Lowdell MW, Craston R, Samuel D, Wood ME, O'Neill E, Saha V, Prentice HG. Evidence that continued remission in patients treated for acute leukaemia is dependent upon autologous natural killer cells. Br J Haematol. 2002 Jun;117(4):821-7.

13) Miller JS, Soignier Y, Panoskaltsis-Mortari A, McNearney SA, Yun GH, Fautsch SK, McKenna D, Le C, Defor TE, Burns LJ, Orchard PJ, Blazar BR, Wagner JE, Slungaard A, Weisdorf DJ, Okazaki IJ, McGlave PB. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood. 2005 Apr 15;105(8):3051-7. Epub 2005 Jan 4.

14) Hayashi T, Hideshima T, Akiyama M, Podar K, Yasui H, Raje N, Kumar S, Chauhan D, Treon SP, Richardson P, Anderson KC. Molecular mechanisms whereby immunomodulatory drugs activate natural killer cells: clinical application. Br J Haematol. 2005 Jan;128(2):192-203.

15) Borg C, Terme M, Taieb J, Menard C, Flament C, Robert C, Maruyama K, Wakasugi H, Angevin E, Thielemans K, Le Cesne A, Chung-Scott V, Lazar V, Tchou I, Crepineau F, Lemoine F, Bernard J, Fletcher JA, Turhan A, Blay JY, Spatz A, Emile JF, Heinrich MC, Mecheri S, Tursz T, Zitvogel L. Novel mode of action of c-kit tyrosine kinase inhibitors leading to NK cell-dependent antitumor effects. J Clin Invest. 2004 Aug;114(3):379-88.

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Welcome to Envita's Biologics Division! Our AAIT method is the latest in our line of cancer and immunotherapy treatments and in comparison to immunotherapy options that are currently available in United States as well as abroad, it boasts a significant level of tumor kill without having to resort to biopsy. AAIT can be used in addition to chemotherapy, radiotherapy and/or delivered intra-operatively. It's very important to note that AAIT can also be utilized completely independent of chemotherapy and radiation because it leverages a completely different mechanism of tumor kill. If you have any questions or would like to speak to our clinicians directly, please send us an email. To learn more about how you or your institution can become part of our Envita Mexico team, please don't hesitate to contact us.

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