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Stage 4 Breast Cancer A New
  Immunotherapy Treatment Brings Hope to
         Stage 4 Cancer Patients




Immunology Strengthens Fight Against Stage 4 cancer and Stage 4
Breast Cancer

The field of cancer immunology is now more than 30 years old and has developed
rapidly, particularly over the last 10 years. Immunotherapy, the use of the stimulated
immune system to fight off disease, has branched out into different subsets including
immune system growth factors, monoclonal antibodies, cellular therapies, and even
combinations of two or more of these immunotherapy strategies. Recent advances in
adoptive immunotherapy (focused on the expansion of specific disease-fighting white
blood cells and their infusion into patients) have led to breakthrough discoveries that will
profoundly impact the treatment of stage 4 breast cancer and other stage 4 cancer over
the next decade.

A Look at Traditional Breast Cancer and stage 4 cancer Protocols

Breast cancer treatment in the early stages has, for quite some time, been focused on
lumpectomy combined with radio and chemotherapy to increase survival. With late
stage or Stage 4 Breast Cancer we typically see more of the same, however, it is not
uncommon to see additional forms of radiotherapy and chemotherapy treatments if the
patient had grown refractory (or is not responding to treatment) to the first regimen.
Immunotherapy for cancer and stage 4 cancer provides a complete new way of
targeting metastasis and dealing with the primary site of the cancer all at one time. Data
clearly shows that as tumors and cancer stages progress so do immune blocking
mechanisms conjured (up regulated) by cancers to self-protect. By depleting such
negative immune factors and rebuilding a specialized cancer vaccine that employs the
body's own natural killer cells to fight - Envita has a powerful and innovative method to
deal with stage 4 breast cancer and stage 4 cancer using the best immunotherapy.

Envita Leads the Field in Stage 4 Breast Cancer Immunotherapy

Multitudes of published studies have demonstrated the effects of adoptive immune
therapy in cancer patients. Envita's renowned medical team assessed the best of these
studies and focused on the strengths and weaknesses of each. Their findings
established a protocol that incorporates only the best procedures for the expansion and
application of cells as a powerful immunotherapy. Our protocols are based on the most
recent published research in the field, from some of the most prestigious hospitals and
universities in the nation and around the world. However, our treatment has been
specially designed to deal specifically with stage 4 breast cancer and stage 4 cancer
patients immune systems.

Cancer Killers for Stage 4 Breast Cancer and Stage 4 Cancer

It is common knowledge among scientists and physicians that three types of white blood
cells can be activated by the immune system to kill cancer cells directly: cytotoxic T
lymphocytes (CTLs), natural killer cells (NKs), and natural killer T cells (NKTs). These
cells are found circulating in the body in low amounts; however, they are a major first-
line immune system cancer defense. As cancer progress these cells can decrease in
number and are often times being blocked by the cancer signaling. This plays an
essential role in the progression of the disease. Envita has found an effective way to
reverse this process.

Stage 4 Breast Cancer Patients and Understanding Natural Killer Cells

Over the past 20 years, scientific studies have repeatedly shown that breast cancer
patients have significantly lower levels of natural killer cells than healthy individuals. 1-3
Additionally, NK and NKT function is observably lower in those with breast cancer,
meaning that the immune system is severely impaired.2-5

Research also shows that progression of disease in these patients is associated with
decreasing NK activity, and that people with a significant family history of breast cancer
had lower NK cell activity than people with minor family history of breast cancer. 4,6 This
strongly suggests that defects in NK activity itself may actually contribute to the onset of
breast cancer.6 Not surprisingly, breast cancer patients typically have low levels of
interferon-gamma, a major growth factor for NK cells that is naturally produced by the
body.3
Natural Killer Cells Vital to Stage 4 Breast Cancer and Stage 4 Cancer
Patients

Despite the impairments in NK and NKT cell number and function seen in cancer
patients, these cells have been successfully expanded from patients via advanced
laboratory techniques - providing the necessary cellular resources for effective
immunotherapy.3,5 Published research from Stanford University, the Mayo Clinic, and
Harvard University has recently illustrated and supported the importance of natural killer
cells and natural killer T cells in patients with cancer.

In fact, adoptive immunotherapy composed of NK cell infusions has the capacity to
cause clinical regressions in patients with non-Hodgkin's lymphoma, Hodgkin's disease,
and leukemia. Moreover, NK cells and cytotoxic T lymphocytes have also been utilized
in breast cancer patients with clinical successes noted. 7,8 In patients with metastatic
breast cancer, NK infusion was well-tolerated and resulted in complete response in 20%
of patients.7 In 6 out of 16 patients infused with activated T lymphocytes, objective
tumor regressions were observed. 8 In animal models of breast cancer, the anti-tumor
effects of agents such as interleukin-2 and interleukin-12 were determined to be
dependent on NK cells. 9,10 Additionally, the presence of activated NK cells and other
tumor-fighting immune cells have proven to be key factors in the response of cancer
patients to drugs such as thalidomide, Gleevec, and paclitaxel. 11-13


Envita's Two-fold Stage 4 Breast Cancer and Stage 4 Cancer
Immunotherapy

Envita Natural Medical Center in its Mexico office is currently utilizing NK cells and
CTLs as immunotherapy Treatment for cancer patients. Envita's proprietary immune
therapy vaccine is called AAIT (for autologous adoptive immune therapy,) and there are
4 major cell types involved - the great majority being natural killer cells and T cells. The
types of cells that make up Envita's treatment are listed below:

• Natural killer cells
• Natural killer T cells
• Cytokine-induced killer cells
• Cytotoxic T lymphocytes

The vaccine(s) is compiled by growing a patient’s own antitumor immune cells into the
billions. These cells are then analyzed for activation markers and tested for their ability
to kill cancer cells in the laboratory, then re-infused into the patient.

Enhancing the immune system is a major benefit to fighting cancer, but this vaccine-
driven routine may be added upon through subtraction. Simply put, we can improve
results by not only bolstering critical components of the immune system, but
simultaneously depleting it of negative factors that impede its functionality. Depleting the
negative factors is extremely important.

It is no secret that cancer cells effect the release of T-regulatory cells, or "negative T
cells." The numbers of these cells correlate directly with specific cancer stages -
respective to each cancer type. The more advanced the cancer, the higher the T-
regulatory cells. These cells block your body’s immune system ability to fight. The
immune system is the first and last defense against cancer.

Naturally, by stepping in and acting to deplete these cells along with other key enzymes
that block critical immune system, cancer cell-killing action will be expedited
exponentially. Imagine your immune system being targeted and ready to go, yet
something in your body suddenly applies the brakes. This is in fact what most stage 4
breast cancer and stage 4 cancer patients are dealing with in regards to high regulatory
T cells. Envita's treatment protocols build a targeted vaccine by using the body's most
powerful cancer killers, but also depletes the portion of the immune system that inhibits
the body from functioning efficiently in such regard.

Case in point, there is no treatment (conventional or alternative) that can be effective in
the later stages of cancer if these negative T-cells are not effectively down-regulated.

Unlike other immune therapies found in the published literature, Envita’s AAIT can be
used as a stand-alone treatment. AAIT can also be given in conjunction with other
therapies that will act to enhance the effects of cells once they are in the patient. This is
a key improvement over many of the published studies in the scientific literature.
Envita’s AAIT therapy is not just focused on expanding cells in the laboratory; the
ultimate goal is to also expand them and keep them activated after they are infused
back into the body. Making AAIT next important piece to stage 4 breast cancer and
stage 4 cancer therapy.

AAIT Available for stage 4 breast cancer at Envita Mexico

The activated natural killer cells in Envita's AAIT are considerably more effective in the
realm of tumor obliteration than other similar treatments offered in Mexico or across the
globe. Backed by scientific research and clinical results, Envita's AAIT offers a powerful
option for Stage 4 Breast Cancer and stage 4 cancer patients who are looking to fight
cancer while keeping their immune system intact. If you have any questions concerning
Envita’s AAIT, please consult with our team of physicians and patient educators. This
particular therapy is offered in Envita Mexico's international cancer center.

References

1)    Balch CM, Tilden AB, Dougherty PA, Cloud GA. Depressed levels of granular
lymphocytes with natural killer (NK) cell function in 247 cancer patients. Ann Surg. 1983
Aug;198(2):192-9.
2)     Konjevic G, Spuzic I. Evaluation of different effects of sera of breast cancer
patients on the activity of natural killer cells. J Clin Lab Immunol. 1992;38(2):83-93.

3)    Caras I, Grigorescu A, Stavaru C, Radu DL, Mogos I, Szegli G, Salageanu A.
Evidence for immune defects in breast and lung cancer patients. Cancer Immunol
Immunother. 2004 Dec;53(12):1146-52.

4)    Garner WL, Minton JP, James AG, Hoffmann CC. Human breast cancer and
impaired NK cell function. J Surg Oncol. 1983 Sep;24(1):64-6.

5)     Crough T, Purdie DM, Okai M, Maksoud A, Nieda M, Nicol AJ. Modulation of
human Valpha24(+)Vbeta11(+) NKT cells by age, malignancy and conventional
anticancer therapies. Br J Cancer. 2004 Nov 29;91(11):1880-6.

6)    Strayer DR, Carter WA, Brodsky I. Familial occurrence of breast cancer is
associated with reduced natural killer cytotoxicity. Breast Cancer Res Treat.
1986;7(3):187-92.

7)     deMagalhaes-Silverman M, Donnenberg A, Lembersky B, Elder E, Lister J,
Rybka W, Whiteside T, Ball E. Posttransplant adoptive immunotherapy with activated
natural killer cells in patients with metastatic breast cancer. J Immunother. 2000
Jan;23(1):154-60.

8)     Bishop MR, Fowler DH, Marchigiani D, Castro K, Kasten-Sportes C, Steinberg
SM, Gea-Banacloche JC, Dean R, Chow CK, Carter C, Read EJ, Leitman S, Gress R.
Allogeneic lymphocytes induce tumor regression of advanced metastatic breast cancer.
J Clin Oncol. 2004 Oct 1;22(19):3886-92.

9)    Divino CM, Chen SH, Yang W, Thung S, Brower ST, Woo SL. Anti-tumor
immunity induced by interleukin-12 gene therapy in a metastatic model of breast cancer
is mediated by natural killer cells. Breast Cancer Res Treat. 2000 Mar;60(2):129-34.

10)    Joshi SS, Tarantolo SR, Kuszynski CA, Kessinger A. Antitumor therapeutic
potential of activated human umbilical cord blood cells against leukemia and breast
cancer. Clin Cancer Res. 2000 Nov;6(11):4351-8.

11)  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.

12)    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.

13)    Kubo M, Morisaki T, Matsumoto K, Tasaki A, Yamanaka N, Nakashima H, Kuroki
H, Nakamura K, Nakamura M, Katano M. Paclitaxel probably enhances cytotoxicity of
natural killer cells against breast carcinoma cells by increasing perforin production.
Cancer Immunol Immunother. 2005 May;54(5):468-76. Epub 2004 Dec 9.

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Stage 4 Breast Cancer A New Immunotherapy Treatment Brings Hope to Stage 4 Cancer Patients

  • 1. Stage 4 Breast Cancer A New Immunotherapy Treatment Brings Hope to Stage 4 Cancer Patients Immunology Strengthens Fight Against Stage 4 cancer and Stage 4 Breast Cancer The field of cancer immunology is now more than 30 years old and has developed rapidly, particularly over the last 10 years. Immunotherapy, the use of the stimulated immune system to fight off disease, has branched out into different subsets including immune system growth factors, monoclonal antibodies, cellular therapies, and even combinations of two or more of these immunotherapy strategies. Recent advances in adoptive immunotherapy (focused on the expansion of specific disease-fighting white blood cells and their infusion into patients) have led to breakthrough discoveries that will profoundly impact the treatment of stage 4 breast cancer and other stage 4 cancer over the next decade. A Look at Traditional Breast Cancer and stage 4 cancer Protocols Breast cancer treatment in the early stages has, for quite some time, been focused on lumpectomy combined with radio and chemotherapy to increase survival. With late stage or Stage 4 Breast Cancer we typically see more of the same, however, it is not uncommon to see additional forms of radiotherapy and chemotherapy treatments if the patient had grown refractory (or is not responding to treatment) to the first regimen.
  • 2. Immunotherapy for cancer and stage 4 cancer provides a complete new way of targeting metastasis and dealing with the primary site of the cancer all at one time. Data clearly shows that as tumors and cancer stages progress so do immune blocking mechanisms conjured (up regulated) by cancers to self-protect. By depleting such negative immune factors and rebuilding a specialized cancer vaccine that employs the body's own natural killer cells to fight - Envita has a powerful and innovative method to deal with stage 4 breast cancer and stage 4 cancer using the best immunotherapy. Envita Leads the Field in Stage 4 Breast Cancer Immunotherapy Multitudes of published studies have demonstrated the effects of adoptive immune therapy in cancer patients. Envita's renowned medical team assessed the best of these studies and focused on the strengths and weaknesses of each. Their findings established a protocol that incorporates only the best procedures for the expansion and application of cells as a powerful immunotherapy. Our protocols are based on the most recent published research in the field, from some of the most prestigious hospitals and universities in the nation and around the world. However, our treatment has been specially designed to deal specifically with stage 4 breast cancer and stage 4 cancer patients immune systems. Cancer Killers for Stage 4 Breast Cancer and Stage 4 Cancer It is common knowledge among scientists and physicians that three types of white blood cells can be activated by the immune system to kill cancer cells directly: cytotoxic T lymphocytes (CTLs), natural killer cells (NKs), and natural killer T cells (NKTs). These cells are found circulating in the body in low amounts; however, they are a major first- line immune system cancer defense. As cancer progress these cells can decrease in number and are often times being blocked by the cancer signaling. This plays an essential role in the progression of the disease. Envita has found an effective way to reverse this process. Stage 4 Breast Cancer Patients and Understanding Natural Killer Cells Over the past 20 years, scientific studies have repeatedly shown that breast cancer patients have significantly lower levels of natural killer cells than healthy individuals. 1-3 Additionally, NK and NKT function is observably lower in those with breast cancer, meaning that the immune system is severely impaired.2-5 Research also shows that progression of disease in these patients is associated with decreasing NK activity, and that people with a significant family history of breast cancer had lower NK cell activity than people with minor family history of breast cancer. 4,6 This strongly suggests that defects in NK activity itself may actually contribute to the onset of breast cancer.6 Not surprisingly, breast cancer patients typically have low levels of interferon-gamma, a major growth factor for NK cells that is naturally produced by the body.3
  • 3. Natural Killer Cells Vital to Stage 4 Breast Cancer and Stage 4 Cancer Patients Despite the impairments in NK and NKT cell number and function seen in cancer patients, these cells have been successfully expanded from patients via advanced laboratory techniques - providing the necessary cellular resources for effective immunotherapy.3,5 Published research from Stanford University, the Mayo Clinic, and Harvard University has recently illustrated and supported the importance of natural killer cells and natural killer T cells in patients with cancer. In fact, adoptive immunotherapy composed of NK cell infusions has the capacity to cause clinical regressions in patients with non-Hodgkin's lymphoma, Hodgkin's disease, and leukemia. Moreover, NK cells and cytotoxic T lymphocytes have also been utilized in breast cancer patients with clinical successes noted. 7,8 In patients with metastatic breast cancer, NK infusion was well-tolerated and resulted in complete response in 20% of patients.7 In 6 out of 16 patients infused with activated T lymphocytes, objective tumor regressions were observed. 8 In animal models of breast cancer, the anti-tumor effects of agents such as interleukin-2 and interleukin-12 were determined to be dependent on NK cells. 9,10 Additionally, the presence of activated NK cells and other tumor-fighting immune cells have proven to be key factors in the response of cancer patients to drugs such as thalidomide, Gleevec, and paclitaxel. 11-13 Envita's Two-fold Stage 4 Breast Cancer and Stage 4 Cancer Immunotherapy Envita Natural Medical Center in its Mexico office is currently utilizing NK cells and CTLs as immunotherapy Treatment for cancer patients. Envita's proprietary immune therapy vaccine is called AAIT (for autologous adoptive immune therapy,) and there are 4 major cell types involved - the great majority being natural killer cells and T cells. The types of cells that make up Envita's treatment are listed below: • Natural killer cells • Natural killer T cells • Cytokine-induced killer cells • Cytotoxic T lymphocytes The vaccine(s) is compiled by growing a patient’s own antitumor immune cells into the billions. These cells are then analyzed for activation markers and tested for their ability to kill cancer cells in the laboratory, then re-infused into the patient. Enhancing the immune system is a major benefit to fighting cancer, but this vaccine- driven routine may be added upon through subtraction. Simply put, we can improve results by not only bolstering critical components of the immune system, but
  • 4. simultaneously depleting it of negative factors that impede its functionality. Depleting the negative factors is extremely important. It is no secret that cancer cells effect the release of T-regulatory cells, or "negative T cells." The numbers of these cells correlate directly with specific cancer stages - respective to each cancer type. The more advanced the cancer, the higher the T- regulatory cells. These cells block your body’s immune system ability to fight. The immune system is the first and last defense against cancer. Naturally, by stepping in and acting to deplete these cells along with other key enzymes that block critical immune system, cancer cell-killing action will be expedited exponentially. Imagine your immune system being targeted and ready to go, yet something in your body suddenly applies the brakes. This is in fact what most stage 4 breast cancer and stage 4 cancer patients are dealing with in regards to high regulatory T cells. Envita's treatment protocols build a targeted vaccine by using the body's most powerful cancer killers, but also depletes the portion of the immune system that inhibits the body from functioning efficiently in such regard. Case in point, there is no treatment (conventional or alternative) that can be effective in the later stages of cancer if these negative T-cells are not effectively down-regulated. Unlike other immune therapies found in the published literature, Envita’s AAIT can be used as a stand-alone treatment. AAIT can also be given in conjunction with other therapies that will act to enhance the effects of cells once they are in the patient. This is a key improvement over many of the published studies in the scientific literature. Envita’s AAIT therapy is not just focused on expanding cells in the laboratory; the ultimate goal is to also expand them and keep them activated after they are infused back into the body. Making AAIT next important piece to stage 4 breast cancer and stage 4 cancer therapy. AAIT Available for stage 4 breast cancer at Envita Mexico The activated natural killer cells in Envita's AAIT are considerably more effective in the realm of tumor obliteration than other similar treatments offered in Mexico or across the globe. Backed by scientific research and clinical results, Envita's AAIT offers a powerful option for Stage 4 Breast Cancer and stage 4 cancer patients who are looking to fight cancer while keeping their immune system intact. If you have any questions concerning Envita’s AAIT, please consult with our team of physicians and patient educators. This particular therapy is offered in Envita Mexico's international cancer center. References 1) Balch CM, Tilden AB, Dougherty PA, Cloud GA. Depressed levels of granular lymphocytes with natural killer (NK) cell function in 247 cancer patients. Ann Surg. 1983 Aug;198(2):192-9.
  • 5. 2) Konjevic G, Spuzic I. Evaluation of different effects of sera of breast cancer patients on the activity of natural killer cells. J Clin Lab Immunol. 1992;38(2):83-93. 3) Caras I, Grigorescu A, Stavaru C, Radu DL, Mogos I, Szegli G, Salageanu A. Evidence for immune defects in breast and lung cancer patients. Cancer Immunol Immunother. 2004 Dec;53(12):1146-52. 4) Garner WL, Minton JP, James AG, Hoffmann CC. Human breast cancer and impaired NK cell function. J Surg Oncol. 1983 Sep;24(1):64-6. 5) Crough T, Purdie DM, Okai M, Maksoud A, Nieda M, Nicol AJ. Modulation of human Valpha24(+)Vbeta11(+) NKT cells by age, malignancy and conventional anticancer therapies. Br J Cancer. 2004 Nov 29;91(11):1880-6. 6) Strayer DR, Carter WA, Brodsky I. Familial occurrence of breast cancer is associated with reduced natural killer cytotoxicity. Breast Cancer Res Treat. 1986;7(3):187-92. 7) deMagalhaes-Silverman M, Donnenberg A, Lembersky B, Elder E, Lister J, Rybka W, Whiteside T, Ball E. Posttransplant adoptive immunotherapy with activated natural killer cells in patients with metastatic breast cancer. J Immunother. 2000 Jan;23(1):154-60. 8) Bishop MR, Fowler DH, Marchigiani D, Castro K, Kasten-Sportes C, Steinberg SM, Gea-Banacloche JC, Dean R, Chow CK, Carter C, Read EJ, Leitman S, Gress R. Allogeneic lymphocytes induce tumor regression of advanced metastatic breast cancer. J Clin Oncol. 2004 Oct 1;22(19):3886-92. 9) Divino CM, Chen SH, Yang W, Thung S, Brower ST, Woo SL. Anti-tumor immunity induced by interleukin-12 gene therapy in a metastatic model of breast cancer is mediated by natural killer cells. Breast Cancer Res Treat. 2000 Mar;60(2):129-34. 10) Joshi SS, Tarantolo SR, Kuszynski CA, Kessinger A. Antitumor therapeutic potential of activated human umbilical cord blood cells against leukemia and breast cancer. Clin Cancer Res. 2000 Nov;6(11):4351-8. 11) 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. 12) 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
  • 6. kinase inhibitors leading to NK cell-dependent antitumor effects. J Clin Invest. 2004 Aug;114(3):379-88. 13) Kubo M, Morisaki T, Matsumoto K, Tasaki A, Yamanaka N, Nakashima H, Kuroki H, Nakamura K, Nakamura M, Katano M. Paclitaxel probably enhances cytotoxicity of natural killer cells against breast carcinoma cells by increasing perforin production. Cancer Immunol Immunother. 2005 May;54(5):468-76. Epub 2004 Dec 9.