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Technology of M.R.

Lentz
The role of therapeutic apheresis in the treatment of cancer: a review

M. Rigdon Lentz
Therapeutic Apheresis. -1999. -Vol. 3, no. 1. -R. 40-48.
Columbia Southern Hills Medical Center, Nashville, Tennessee, U.S.A.

Scientific background
Many cancer cells are known to actively overproduce and shed receptors of
certain cytokines, to protect themselves from the immune system. The two
soluble TNF receptors R1 and R2 are shed by cancer cells to protect
themselves from the cytokine "Tumor Necrosis Factor" (TNF) expressed by
immuneactive cells. TNF is an important and effective cytokine expressed by
immune cells to kill cancer (and other) cells. The BioPheresis system is
designed to remove these inhibitors TNF-R1 and TNF-R2 so that the immune
system can more effectively attack the cancer. Work of Dr. M. Rigdon
Lentz et al. regarding the TNF receptor shedding as a mechanism, whereby
cancer cells may protect themselves from otherwise normal destructive
immune surveillance is the basis for this approach. Other scientists have
since shown that elevation of these receptor levels in blood is an
independent variable that correlates with reduced patient survival regardless
of tumor type and stage (Langkorf et. al). The applications "Ultrapheresis"
and "Immune adsorption" were both developed by Dr. Lentz and his
colleagues in an attempt to remove these inhibitors to allow normal immune
function against cancer.

Normal immune sensitive cells (for example, viral infected cells, transplanted
cells) express receptors to TNF (TNF-R1 and TNF-R2) on their cell surface
and are sensitive to the cytotoxic effect of TNF that is brought to this target
cell by a family of immune active cells. It is believed that cancer cells
overproduce these receptors to the point that they are shed into the tumor
microenvironment and can bind to the TNF of an active killer cell and
neutralize it. A killer cell once neutralized should no longer kill the cancer
target (see figure 1).

Normally immune sensitive cell


Figure 1: in comparison to normally immune sensitive cells, cancer cells
express a high level of TNF receptors to the point they are shed into the
tumor.

The Plasmapheresis system is designed to remove these inhibiting sTNFRs,


allowing the body's own TNF mediated immune response to become
unblocked and shall enable it to attack and destroy tumors (see figure 2).

TNF is blocked by the


Low inhibitor levels allow
inhibitors TNF-R1 and TNF-
TNF to attack cancer cells
R2

TNF blocked by inhibitors Unblocked TNF


TNF-R1
TNF-R2

Blocked TNF ist rendered Uninhibited or "Free" TNF is


Inactive in attack against able to launch effective
cancer cells attack on cancer cells

Figure 2: Hypothesis for TNF and sTNFR Interactions

THERAPEUTIC PLASMAPHERESIS PROTOCOLS IN ONCOLOGY


Valery Voinv.A., Orlov, S.v., Karchevskyy K.s., Warriors A.v.
Spbmu name akad. I.p. Pavlova, St. Petersburg.
There is a lot of evidence for detoxification and efferent therapy in cancer patients:
1. in the preoperative preparation of the 2-3 sessions of plasmapheresis with laser
irradiation of blood. Especially in cases with obstructive jaundice and inflammatory
complications from tumors.
2. support of chemoradiotherapy-plasmapheresis sessions over 5, 10, 15 and 20
sessions of radiation for a month.
3. accompanying courses of chemotherapy for the purpose of detoxication-the 2-3
sessions of plasmapheresis in volume of up to 0.3 ORC with laser irradiation of blood
after each cycle of chemotherapy. Substitution of kristalloidnymi solutions,
expressed in gipoproteinemii to add protein solutions (albumin, plasma). A total of
over 6 months may take up to 12-15 sessions of plasmapheresis.
4. intensive plasmapheresis programs conducted through the day during the month
(up to 12 sessions) with the removal of up to 0.5 ORC and replacement with donor
plasma/w ratio of 0.8: 1 with laser irradiation of blood for inhibitors of killernoj
activity of lymphocytes and killer cytolytic activity of macrophages to activate
cellular immunity.
(Published in the Anthology: "proceedings of the twelfth Conference of the Moscow
society of gemafereza, m., 2004, p. 9).

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