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CHAPTER 22  ■  Lymphoid and Plasma Cell Neoplasms                                  439














                                                       Battery




                                                                         Normal              Patient           Blank               Patient

                                                                          serum               serum                                  urine



                                                        Albumin                                                                                                     Albumin





                                             Alpha globulins                                                                                                                   Monoclonal          Gamma
                                                                                                                                                                               (“M-protein”)       globulins

                                                                                                                                                                               spike

                                               Beta globulins
                                                                                                             Monoclonal                                                        Beta
                                                                                                                protein                                                        globulins

                                                                                                            (“M-protein”)
                                                                                                                                                                               Alpha

                                          Gamma globulins                                                                                                                      globulins









                                                                    Serum initially           Direction of                     Urine initially            Patient

                                                                    placed here               protein migration                placed here                serum
                                                                                              in electrical field

                                       FIGURE 22.20  Protein electrophoresis in pl  s     cell   ise  se. Seru   or urine is pl  ce     t one en   o     strip o

                                       gel,   cross which   n electric  l current is   pplie  . Most proteins h  ve    neg  tive ch  rge   n     igr  te tow  r   the

                                       positive pole   t v  rious spee  s   ccor  ing to their   olecul  r weight   n   ch  rge. T e seru   on the le   shows
                                       n  rrow b  n   in the g         globulin region. Seru   protein h  s spille   into urine, which   e  onstr  tes        tching

                                       b  n  . In the sc  n o  p  tient seru   on the right, the height o  the tr  cing is proportion  l to the     ount o  protein

                                       st  ine   in e  ch b  n  . Monoclon  l protein   ppe  rs   s    t  ll, n  rrow (  onoclon  l) “M-protein.” (Reprinte    ro

                                       McConnell   H. T e Nature o  Disease Pathology  or the Health Pro essions, Phil    elphi  , PA: Lippincott Willi    s
                                       & Wilkins, 2007, with per  ission.)





                   Em erging Therapies                                                                                               t  rgeting  tu  or  cells    n    e  ectively    e  i  tes  killing


                     re  t  ent o  newly   i  gnose     n   rel  pse     yelo     is                                                o   CD38-neg  tive–be  ring  pl  s      cells  vi      ntibo  y-

                   r  pi  ly exp  n  ing f el   bec  use o  i  prove   un  erst  n  ing                                               epen  ent  cell-  e  i  te    cytotoxicity  (ADCC)    n

                   o    ise  se biology   n     ccess to new   rugs. When “novel”                                                    poptosis. D  r tu  u    b is the   ost   ctive   onoclon  l

                     gents,  i    uno  o  ul  tory    gents  (IMiDs),    n    prote  se                                              ntibo  y in clinic  l tri  ls.

                   inhibitors (PIs) entere   the f el        ec    e   go, they were con-                                      ■   Elotuzu    b is    hu    nize     nti-SLAMF-7   ntibo  y th  t

                   si  ere   s   er in co  bin  tions with gre  ter e  c  cy.                                                       t  rgets the cell sur   ce glycoprotein CS1 on the   yelo

                        Rese  rch is now exten  ing to p  tients who   re experienc-                                                cell   n   on NK cells resulting in   ctiv  tion o  the NK cells.

                   ing    rel  pse. Recent ph  se 3   rug tri  ls suggest th  t co  bi-                                             It exerts   nti  yelo     e  ect vi   ADCC in   yelo     cell

                   n  tions o  new   gents with e  ch other or with   lkyl  tor-b  se                                               lines   n     yelo     cells.

                   ther  py pro  uce    response with   ore i  p  ct   n   prolonge                                            ■   Nivolu    b is   n ex    ple o     novel   rug th  t is b  se   on

                     ur  tion  o   re  ission    n    over  ll  surviv  l.  V  rious  novel                                         the   ssu  ption th  t progr      e     e  th 1 (PD-1) p  thw  y

                   co  bin  tion ther  pies   re e  erging  or rel  pse     yelo                                                    serves   s    checkpoint to li  it   -cell–  e  i  te   i    une

                   p  tients (see Box 22.4).                                                                                        responses. PD-1–blocking   ntibo  ies h  ve been use   to
                                                                                                                                    enh  nce i    unity in soli   tu  ors   n   obt  in   ur  ble

                                                                                                                                    clinic  l responses with   n   ccept  ble s   ety prof le. PD-1
                   IMMUNE APPROACHES                                                                                                eng  ge  ent     y represent one   e  ns by which tu  ors


                                                                                                                                    ev    e i    unosurveill  nce.
                   A  newer  tre  t  ent  che  oi    unother  py  w  s  intro-                                                 ■   A  optive  cellul  r  ther  py  consists  o   chi  eric    nti-

                    uce   in 2000. T is str  tegy incorpor  tes v  rious i    une                                                   gen  receptor  (CAR)      cells  or  regul  tory    -cell

                    ppro  ches:                                                                                                     interventions.




                                                                                                                                    Chi  eric    ntigen  receptor  (CAR)      cells  represents
                   Antibodies
                                                                                                                               process o    o  i ying   utologous    cells with CARs   g  inst


                   ■   D  r  tu  u    b is    hu    nize     nti-CD38   ntibo  y. It                                           CD19   s    ther  peutic str  tegy  or   yelo     by co  bining

                          cts through   ultiple   ech  nis  s o    ction by   irectly                                           utologous    cells with   nti-CD CAR.
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